PMCID
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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In the subgroup with larger tumor sizes (> 4.75 cm), GIST patients exhibiting lower LARP7 expression experienced longer PFS times (Fig. 4B).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A nomogram was developed based on LARP7 expression, tumor size, mitotic counts, and gender to predict the risk of recurrence of GIST after treatment, which may assist in guiding patient selection for therapy (Fig. 4C).Fig.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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4Elevated expression levels of LARP7 were indicative of an unfavorable prognosis in GIST located in the small intestine. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Kaplan-Meier survival curves comparing PFS of GISTs across various demographic and clinical parameters, including age, gender, tumor location, tumor size, mitotic count, mutation status, and classifications according to NIH and WHO consensus criteria. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Kaplan-Meier survival curves illustrating PFS in subgroups with high versus low LARP7 expression in small intestine GISTs and those with large tumor size. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A nomogram integrating LARP7 expression with additional clinical characteristics for GIST prognostication.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Fig. 4 Elevated expression levels of LARP7 were indicative of an unfavorable prognosis in GIST located in the small intestine. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Kaplan-Meier survival curves comparing PFS of GISTs across various demographic and clinical parameters, including age, gender, tumor location, tumor size, mitotic count, mutation status, and classifications according to NIH and WHO consensus criteria. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Kaplan-Meier survival curves illustrating PFS in subgroups with high versus low LARP7 expression in small intestine GISTs and those with large tumor size. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A nomogram integrating LARP7 expression with additional clinical characteristics for GIST prognostication.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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To investigate the mechanisms by which elevated LARP7 promoted the GIST process, we incorporated an additional GIST transcriptome dataset that includes more GIST tumors, expanding our analysis beyond GSE155800.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Differential expression analysis was conducted independently between the LARP7-high and LARP7-low groups across the GSE225819, GSE136755, and Proteomics (Sun et al.) datasets.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Ultimately, several differentially expressed genes and proteins were identified: in GSE225819, 73 were up-regulated and 48 down-regulated; in GSE136755, 197 were up-regulated and 72 down-regulated; and in the Proteomic (Sun et al.) dataset, 178 were up-regulated and 44 down-regulated (Fig. 5A and Table S3).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A total of 31 DEGs were found to be consistently increased or decreased across the two transcriptome datasets, of which 28 up-regulated DEGs were primarily enriched in interferon signaling and the negative regulation of viral processes (Fig. 5B).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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When intersected with the DEPs, only GBP1 was elevated in the LARP7-high group at both mRNA and protein levels (Fig. 5C and D).Fig.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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5Functional enrichment results of LARP7 in GIST. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The intersection of differentially expressed genes/proteins between the high and low LARP7 expression groups in the three datasets, GSE225819, GSE136755, and the Proteomics (Sun et al.) dataset. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Functional enrichment network for 27 commonly up-regulated genes in GSE225819 and GSE136755 using ClueGO. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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C-D) Boxplots and point plot showing GBP1 highly expressed in the LARP7-high group and significantly positively correlated with LARP7 at both mRNA and protein levels. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Barplot summarizing the functional enrichment results of up-and down-regulated genes/proteins in the three datasets. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Venn plot illustrating the intersection of functional enrichment results for three up-regulated genes/proteins. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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G-H) Lollipop plots depicting the 16 common pathways in GSE225819 and GSE136755, as well as the four common pathways in GSE225819 and the Proteomics (Sun et al.) dataset.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Fig. 5 Functional enrichment results of LARP7 in GIST. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The intersection of differentially expressed genes/proteins between the high and low LARP7 expression groups in the three datasets, GSE225819, GSE136755, and the Proteomics (Sun et al.) dataset. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Functional enrichment network for 27 commonly up-regulated genes in GSE225819 and GSE136755 using ClueGO. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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C-D) Boxplots and point plot showing GBP1 highly expressed in the LARP7-high group and significantly positively correlated with LARP7 at both mRNA and protein levels. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Barplot summarizing the functional enrichment results of up-and down-regulated genes/proteins in the three datasets. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Venn plot illustrating the intersection of functional enrichment results for three up-regulated genes/proteins. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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G-H) Lollipop plots depicting the 16 common pathways in GSE225819 and GSE136755, as well as the four common pathways in GSE225819 and the Proteomics (Sun et al.) dataset.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Functional enrichment analysis was then conducted on these DEGs/DEPs.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The results indicated that the up-regulated genes in GSE225819, GSE136755, and Proteomic (Sun et al.) datasets were enriched in 33, 410, and 227 pathways, respectively, while the down-regulated genes were enriched in 2, 9, and 38 pathways, respectively (Fig. 5E and Table S4).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The intersection of up-regulated DEGs/DEPs showed high expression of LARP7 may promote an immune response to viruses or other microbial threats, including pathways such as interferon signaling, loading of antigenic peptides onto class I MHC, antigen processing and presentation, and T cell-mediated cytotoxicity (Fig. 5F–H).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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These findings suggested that LARP7 may play a role in antiviral response in GISTs.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Tumors are typically surrounded by an immune microenvironment, crucial in influencing tumor growth, metastasis, and drug resistance.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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To investigate potential differences in immune cell infiltration between GISTs with high and low LARP7 expression, we employed TIMER 2.0 to calculate the ratios of immune cell types.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The fractions of CD8+ T cells and CD8 effector memory T cells were both found to be elevated in the high LARP7 expression groups within datasets GSE136755 and GSE225819.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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NK cells and M1 Macrophages were also increased in the high LARP7 group in one of the datasets.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Conversely, the levels of monocytes, neutrophils, and other immune cells were reduced in the low LARP7 group in GSE136755 (Fig. 6A).Fig.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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6Immune cell infiltration analysis and cytokine pathway status prediction. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Boxplots showing the difference in immune cell infiltration levels in GSE136755 and GSE225819. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Heatmaps displaying the status of cytokine and chemokine-related pathways (characterized by CytoSig_zscore). (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Boxplots indicating IFN1, IFNG, and IL27 pathway's CytoSig_zscores in GSE136755 and GSE225819.Fig.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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6 Immune cell infiltration analysis and cytokine pathway status prediction. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Boxplots showing the difference in immune cell infiltration levels in GSE136755 and GSE225819. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Heatmaps displaying the status of cytokine and chemokine-related pathways (characterized by CytoSig_zscore). (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Boxplots indicating IFN1, IFNG, and IL27 pathway's CytoSig_zscores in GSE136755 and GSE225819.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The preceding findings indicated a potential association between LARP7 and the expression of IFN-related genes.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Therefore, we utilized "CytoSig" to evaluate the activation status of pathways involving various cytokines and chemokines (Fig. 6B).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A comparison between the high and low LARP7 expression groups revealed significant activation of the IFNG, IFN1, and IL27 pathways in the high-expression group (Fig. 6C).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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These findings corroborated the results of the functional enrichment analysis.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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We utilized the ENCORI database to investigate of the regulatory mechanisms governing LARP7 within the intricate cellular milieu enriched with miRNAs and lncRNAs.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Our analysis of the miRNA-target network identified nine miRNAs (hsa-miR-138–5p, hsa-miR-452–5p, hsa-miR-485–5p, hsa-miR-758–3p, hsa-miR-942–5p, hsa-miR-3140–3p, hsa-miR-3163, hsa-miR-4676–3p, and hsa-miR-5586–5p) that directly targeted the LARP7 mRNA (Table S5).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Together with hsa-miR-892c-3p and hsa-miR-6884–5p, these miRNA collectively form a small network involving LARP7, FAM107B, CCNG1, CDK13, and TMEM184A (Fig. 7A).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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We downloaded the GIST miRNA dataset GSE85091 for further screening (Fig. 7B).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Notably, hsa-miR-138–5p was significantly down-regulated in GISTs (Fig. 7C), suggesting its potential role in the regulation of LARP7 expression.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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To explore the lncRNAs targeting hsa-miR-138–5p, we identified 32 lncRNAs from the ENCORI database.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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By intersecting these with the significantly up-regulated lncRNAs in GSE155800 (Fig. 7D), we identified two lncRNAs (H19 and LINC00665) (Fig. 7E).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Both H19 and LINC0065 were found to be up-regulated in GISTs compared to normal tissues (Fig. 7F), potentially influencing LARP7 expression through the regulation of hsa-miR-138–5p.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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In conclusion, we identified a lncRNA (H19 or LINC00665)-miRNA (hsa-miR-138–5p)-mRNA (LARP7) axis, which may play a significant role in the tumorigenesis and progression of GIST.Fig.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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7Construction of regulatory network around LARP7. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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miRNA-mRNA regulatory network. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Volcano plot illustrating differentially expressed miRNAs between GISTs and normal tissues in GSE85091. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Violin plot indicating hsa-miR-138–5p expression in GISTs and normal tissues. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Volcano plot depicting differentially expressed lncRNAs between GISTs and normal tissues in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Venn diagram showing the intersection between lncRNAs predicted in the ENCORI database and up-regulated lncRNAs in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Violin plot illustrating the expression of lncRNAs H19 and LINC00665 between GISTs and normal tissues in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Protein-protein interaction network generated by STRING. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Point plot displaying the co-expression results of proteins in the PPI network for GIST. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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RBPs-LARP7 and LARP7-RNAs regulatory network.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Fig. 7 Construction of regulatory network around LARP7. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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miRNA-mRNA regulatory network. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
|
Volcano plot illustrating differentially expressed miRNAs between GISTs and normal tissues in GSE85091. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Violin plot indicating hsa-miR-138–5p expression in GISTs and normal tissues. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
|
Volcano plot depicting differentially expressed lncRNAs between GISTs and normal tissues in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Venn diagram showing the intersection between lncRNAs predicted in the ENCORI database and up-regulated lncRNAs in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Violin plot illustrating the expression of lncRNAs H19 and LINC00665 between GISTs and normal tissues in GSE155800. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Protein-protein interaction network generated by STRING. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
|
Point plot displaying the co-expression results of proteins in the PPI network for GIST. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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RBPs-LARP7 and LARP7-RNAs regulatory network.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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In the context of the protein-protein interaction network, the STRING database indicated that LARP7 interacted with MEPCE, HEXIM1, and HEXIM2 within the 7SK snRNP complex, as documented in reference (Fig. 7G).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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When the 7SK snRNP complex binded to the Positive Transcription Elongation Factor b (P-TEFb), which comprised cyclin-dependent kinase 9 (CDK9) and its regulator subunit Cyclin T (CCNT1 or CCNT2), it suppressed the active state of P-TEFb.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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This inhibited the activity of RNA polymerase II, thereby preventing excessive gene transcription.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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DDX21 and Tip110 (SART3) facilitated the release of P-TEFb from the 7SK snRNP complex.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Once inactive P-TEFb was released, Brd4 or SEC recruited monomerized Cdk9 and CycT1 to reassemble the core .
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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PPM1 G bond to 7SK RNA and Hexim1 to block P-TEFb assembly into the 7SK snRNP .
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Co-expression analysis revealed that MEPCE, DDX21, and SART3 expression were significantly correlated to LARP7 in GIST (Fig. 7H).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Given that LARP7 was an RNA-binding protein, we examined the LARP7-binding RNAs in ENCORI and identified 763 RNAs.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Conversely, we discovered that 80 RBPs may target LARP7 mRNA (Fig. 7I and Table S6).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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In summary, LARP7 played a crucial role in GIST's substantial regulatory network.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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The clinical application of targeted KIT/PDGFRA kinase inhibitors, such as imatinib, has significantly improved the 5-year survival rates of patients with GIST.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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However, the widespread emergence of drug resistance presents a substantial challenge for these patients.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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An analysis of the GSE132542 transcriptome data revealed that LARP7 expression was elevated in the imatinib-resistant group compared to the imatinib-sensitive group (Fig. 8A).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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In another transcriptome dataset, GSE51697, which included samples from tumor-associated macrophages in untreated GIST patients, imatinib-sensitive patients, and imatinib-resistant patients, LARP7 expression showed a notable decrease in the sensitive group compared to the untreated group.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Although this difference was not statistically significant, there appeared to be a trend toward lower LARP7 expression in the sensitive group than in the resistant group (Fig. 8B).
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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This trend was not reflected at the protein level (Fig. 8C), potentially due to a limited sample size.
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Fig. 8Imatinib resistance analysis and drug sensitivity prediction. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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A-C) Boxplots depicting the expression levels of LARP7 among untreated, imatinib-sensitive, and imatinib-resistant GIST patients in GSE132542, GSE51697, and Proteomics (Sun et al.). (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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D-E) Box plot and point plot showing the relationship between the predicted IC50 values of UMI-77 and LARP7 expression in GSE225819. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Box plot displaying the top 10 drugs with predicted IC50 values significantly lower in the LARP7 high-expression group in GSE136755. (
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PMC11867541
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Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
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Point plot indicating the top 10 drugs whose predicted IC50 values were negatively correlated with LARP7 in GSE136755.Fig.
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