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PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
164,210, Wuhan Pricella Biotechnology Co., Ltd., Wuhan, China) at 37 ℃ in 5 % CO2.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Three siRNA and scrambled sequence vectors were procured from Guangzhou RiboBio Co., Ltd. (China).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The sequences used were as follows: siLARP7–1: GGAGAAAGTTAATGCAACA; siLARP7–2: GCTGGAAACTCGAGATCCT; siLARP7–3: GCGAATGGATGGATTTGAA.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
GIST-T1 and GIST-882 cells were transfected with these siRNAs and scrambled vectors utilizing the RiboFECT™ CP Transfection Kit (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
R10035.8, Guangzhou RiboBio Co., Ltd., Guangzhou, China), following the manufacturer's protocol.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
In brief, 20 nM siRNA was added to the cell medium under serum-free conditions.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The tissues and cells were collected for RNA isolation using TRNzol (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
DP424, TIANGEN, Beijing, China).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Subsequently, the RNA was reverse transcribed into cDNA using the RevertAid First Strand cDNA Synthesis Kit (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
K1622, Thermo, US).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
qRT-PCR was performed using PCR equipment (StepOnePlus, ABI, US), with expression levels normalized to the GAPDH gene.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The primer sequences used were as follows: LARP7: Forward (F): 5'-AGCCAACAGGGAAGAGTGTC-3', Reverse (R): 5'-TGCCAAAGTATCCCGGACTT-3'; GAPDH: F: 5'-GAAGGTGAAGGTCGGAGTC-3', R: 5'-GAAGATGGTGATGGGATTTC-3'.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The cold RIPA buffer, supplemented with a protease inhibitor cocktail (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
R0020, Beijing Solarbio Science & Technology Co., Ltd., Beijing, China), was added to phosphate-buffered saline (PBS) washed cells for lysis.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Total protein was quantified by the Bicinchoninic Acid (BCA) quantification Kit (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
PC0020, Beijing Solarbio Science & Technology Co., Ltd., Beijing, China), following the manufacturer's protocol.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The lysate was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and subsequently transferred to the polyvinylidene fluoride (PVDF) membrane.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
After incubation with primary antibodies at 4 ℃ overnight, the membrane was washed three times with PBS and exposed to the corresponding HRP-conjugated secondary antibodies.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Enhanced chemiluminescence (ECL) was applied to the membrane after the secondary antibody was removed to detect the bands using the Tanon 5200 Multi multifunction imaging system (Shanghai Tanon Bioscience Co., Ltd., Shanghai, China).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
ImageJ (NIH) was utilized for gray-scale value analysis.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Antibody information includes LARP7 (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
17,067–1-AP, Proteintech, Wuhan, China, dilution 1:2000), GAPDH (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
60,004–1-Ig, Proteintech, 1:10,000), HRP-goat anti-mouse recombinant secondary antibody (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
ZB-2305, ZSGB-BIO, Beijing, China, 1:10,000), and HRP-goat anti-rabbit recombinant secondary antibody (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
ZB-2301, ZSGB-BIO, 1:10,000).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
GIST-T1 or GIST-882 cells (5 × 10) were seeded into 96-well plates.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
At 24, 48, 72, and 96 h post-transfection, the medium was replaced with CCK8 solution (Cat.:
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Beyotime Biotech Inc., Shanghai, China) and incubated for 2–3 h. The optical density was measured at 450 nm for each sample.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Relative cell viability was calculated using the following formula: Relative cell viability (%) = (OD450′ / avg (OD450C')) ×100 %.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
GIST-T1 or GIST-882 cells (3 × 10) were seeded into 6-well plates and transfected with siLARP7–2 and a scrambled vector.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
After the cells had adhered, sterile pipette tips (1 mL scale) were used to create a monolayer scratch.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Images were captured at 0 h and 48 h post-scratch and analyzed using ImageJ. The rate of wound healing was calculated using the formula: (scratch area at 0 h – scratch area at 48 h) / scratch area at 0 h × 100 %.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
All analysis and visualization tasks were performed using R (version 4.3.2).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Comparisons between the two groups were conducted using t-tests or paired t-tests, while differences among multiple groups were assessed using ANOVA.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A p-value of <0.05 was considered statistically significant in all comparisons.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Transcriptome and proteome data were collected from the GEO database, and relevant studies to identify the critical genes involved in GIST tumorigenesis.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Differential expression analysis was performed to identify the differentially expressed genes (DEGs) at the mRNA level in datasets GSE155800 and GSE225819 (Fig. 1A and Table S1A, 1B).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Following the separate intersection of up-regulated and down-regulated DEGs at the transcriptional level with the differentially expressed proteins (DEPs), a total of 191 up-regulated DEGs/DEPs and 281 down-regulated DEGs/DEPs were identified (Fig. 1B and Table S1C).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Functional enrichment analysis revealed that the up-regulated DEGs/DEPs were primarily enriched in pathways such as Platelet activation signaling and aggregation, regulation of MAP kinase activity, and Gbeta: gamma recruits PI3 K gamma (Fig. 1C and Table S2A).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The down-regulated DEGs/DEPs were enriched in pathways including the PPAR signaling pathway, cell-cell junction, cellular amino acid metabolic process, and Glycolysis/Gluconeogenesis (Figure S1A and Table S2B).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Additionally, when combined with survival information from the proteomic samples (Fig. 1D), it was found that 35 up-regulated DEGs/DEPs were negatively correlated with PFS (Fig. 1E and Table S1D), while 176 down-regulated DEGs/DEPs were positively correlated with PFS (Figure S1B and Table S1D).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Thus, crucial genes involved in GIST tumorigenesis and prognosis were identified.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Fig. 1Identification of crucial genes in GIST. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Volcano plots depicting DEGs/DEPs in the GSE225819, GSE155800, and Proteomic (Sun et al.) datasets.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The violet points represented significantly up-regulated genes/proteins, while the light-green points represented significantly down-regulated genes/proteins. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Venn plots illustrating up-regulated and down-regulated DEGs/DEPs, respectively. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A functional enrichment network of 191 commonly up-regulated DEGs/DEPs analyzed by ClueGO. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A schematic diagram of gene filtering. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A point plot displaying prognosis-related genes in the up-regulated group.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The point color indicated the absolute value of log2(fold change) for each gene/protein, and point size reflected the value of -log10(p value).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The bar plot in the left panel represented the relationship with of each protein with PFS .Fig.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
1 Identification of crucial genes in GIST. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Volcano plots depicting DEGs/DEPs in the GSE225819, GSE155800, and Proteomic (Sun et al.) datasets.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The violet points represented significantly up-regulated genes/proteins, while the light-green points represented significantly down-regulated genes/proteins. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Venn plots illustrating up-regulated and down-regulated DEGs/DEPs, respectively. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A functional enrichment network of 191 commonly up-regulated DEGs/DEPs analyzed by ClueGO. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A schematic diagram of gene filtering. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A point plot displaying prognosis-related genes in the up-regulated group.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The point color indicated the absolute value of log2(fold change) for each gene/protein, and point size reflected the value of -log10(p value).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The bar plot in the left panel represented the relationship with of each protein with PFS .
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
We focused on the up-regulated DEGs/DEPs linked to unfavorable outcomes, subsequently refining the gene lists.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Univariate Cox regression analysis was then performed to assess the OS and PFS rates for 35 genes.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The results indicated that both LARP7 and FKBP10 were significantly associated with poor prognosis in two analyses (hazard ratio (HR) > 1 and p < 0.05) (Fig. 2A and B).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The Kaplan-Meier method was conducted to analyze the survival difference between high-and low-expression groups, separated by the median expression level of LARP7.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
GIST patients with elevated LARP7 expression experienced shorter survival times (log-rank p = 0.033) (Fig. 2C), and a small GIST transcriptome dataset (GSE112) partially supported this observation (Fig. 2D).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
High expression levels of LARP7 indicated a worse prognosis for GIST patients, coupled with its potential role in crucial mechanisms such as transcriptional regulation, prompting us to conduct a more in-depth investigation into this gene.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Fig. 2LARP7 was associated with a high risk of disease progression. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A-B) Univariate Cox regression results for up-regulated DEGs/DEPs based on OS and PFS, with proteins having p < 0.05 highlighted in rose red. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Kaplan-Meier curves for LARP7 and FKBP10, with the high-expression group shown in red and the low-expression group in blue (grouped by median protein expression). (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Kaplan-Meier curves for LARP7 in GSE112.Fig.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
2 LARP7 was associated with a high risk of disease progression. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A-B) Univariate Cox regression results for up-regulated DEGs/DEPs based on OS and PFS, with proteins having p < 0.05 highlighted in rose red. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Kaplan-Meier curves for LARP7 and FKBP10, with the high-expression group shown in red and the low-expression group in blue (grouped by median protein expression). (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Kaplan-Meier curves for LARP7 in GSE112.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Tumors in GIST patients can arise in various locations within the digestive tract, with most GISTs typically associated with mutations in genes such as KIT and PDGFRA.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Global comparison results indicated that LARP7 was significantly up-regulated in GIST tumor tissues compared to peri‑tumor tissues at both mRNA and protein levels (Fig. 3A).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Based on pathological features such as tumor size, grade, location, and metastasis status, the NIH classified patients into four risk groups: very low risk, low risk, intermediate risk, and high risk.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
The LARP7 protein level was significantly higher in the high risk group than in the very low and low risk groups; however, no significant differences were observed among the four risk groups at the mRNA level (Fig. 3B).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Additionally, the WHO-high group exhibited higher LARP7 levels than the WHO-low group (Fig. 3C).Fig.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
3GISTs classified within the high-risk group demonstrated elevated expression of LARP7. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Violin plots illustrating differential expression of LARP7 between GISTs and normal tissues at both mRNA and protein levels. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots depicting LARP7 expression across various NIH risk groups. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplot comparing LARP7 expression difference between “High” and “Low” WHO-risk groups. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots presenting variations of LARP7 expression in GISTs located in esophagus, stomach, duodenum, small intestine, and colorectum. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots showcasing differences in LARP7 expression in GISTs with KIT or PDGFRA mutations compared to wild-type.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Fig. 3 GISTs classified within the high-risk group demonstrated elevated expression of LARP7. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Violin plots illustrating differential expression of LARP7 between GISTs and normal tissues at both mRNA and protein levels. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots depicting LARP7 expression across various NIH risk groups. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplot comparing LARP7 expression difference between “High” and “Low” WHO-risk groups. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots presenting variations of LARP7 expression in GISTs located in esophagus, stomach, duodenum, small intestine, and colorectum. (
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Boxplots showcasing differences in LARP7 expression in GISTs with KIT or PDGFRA mutations compared to wild-type.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
When GISTs were categorized by tumor location, results revealed that LARP7 expression was more remarkable in esophageal GISTs than in gastric GISTs and colorectal GISTs at the protein level (Fig. 3D).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
LARP7 expression did not vary among subgroups based on tumor grade, tumor histology, or gender (Figure S2A, 2B, 2F).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Correlation analyses indicated a fragile association between LARP7 expression and tumor size, mitotic count (Figure S2C, 2D), and patient age (Figure S2 G).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Although no significant difference in LARP7 protein expression was found between the KIT-mutated and PDGFRA-mutated subgroups (Fig. 3E), LARP7 mRNA was highly expressed in the KIT-high group compared to the KIT-low group in the GSE17743 dataset (Figure S2E).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
We further investigated the correlation between LARP7 expression and prognosis across various demographic factors.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Initially, GIST patients were categorized based on age (median: 58 years), gender, tumor location, tumor size (median: 4.75 cm), mitotic count (median: 3), mutation type, NIH consensus criteria, and WHO consensus criteria.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Kaplan-Meier curves revealed that male GIST patients were at a higher risk of disease progression.
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
Additionally, patients with larger tumor volumes, elevated mitotic counts, or classified as “High” risk according to NIH or WHO criteria at the time of initial diagnosis exhibited poorer outcomes (Fig. 4A).
PMC11867541
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors
A comparison of the survival status between high and low LARP7 expression (based on the median) led to an unexpected finding: among patients with esophageal, gastric, duodenal, and small intestinal GISTs, only those with high LARP7 expression in the small intestine demonstrated significantly worse clinical outcomes (Fig. 4B, Figure S3).