OTAR3088/BioData-CL_Article-Sentences · Datasets at Hugging Face

PMCID string	Title string	Sentences string
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	We explored the mechanism of IGF2 in imatinib resistance in GISTs and whether IGF2 enhanced metastasis and imatinib resistance by driving glycolysis by targeting IGF1R signaling transduction.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF2, identified as an imprinted gene, exhibits a significant impact on cancer progression when its imprinting is lost or relaxed, leading to heightened autocrine IGF2 levels and increased secretion in malignant cells.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Numerous studies have revealed the upregulation of IGF2 in various cancers such as hepatocellular carcinoma, correlating with resistance to chemotherapy and a poorer prognosis[12-14].
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Our investigation, which focused on DEGs associated with liver metastasis and drug resistance in GISTs, we observed elevated levels of IGF2 in GISTs cases linked to liver metastasis and drug resistance.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Our comprehensive analysis included assessment of cell proliferation, viability, migration, and invasiveness.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	The findings strongly suggest that overexpression of IGF2 induce the proliferation, metastasis, and EMT of GIST cells.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF1R, is a tyrosine kinase receptor that can be triggered by IGF2 and has a pivotal role in regulating mammalian development, metabolism, and growth.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF1R is known to be upregulated in various human solid tumors.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Its involvement in cell promoting cell proliferation and inhibiting programmed cell death is facilitated by activation of its tyrosine kinase and the subsequent engagement of the Ras/Raf/MEK and PI3K/AKT/mTOR signaling pathways.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	The IGF2-IGF1R signaling axis assumes critical significance in governing cell proliferation, differentiation, EMT, migration, drug resistance, and maintaining stemness in malignancies.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	This investigation further demonstrated the activation of IGF1R signaling by IGF2 in GIST cells.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	It highlights the role of IGF2 as a pivotal chromatin factor that controls the expression level of IGF1R and modulates downstream signaling by the PI3K/AKT pathway.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF2 also upregulated the expression of glycolytic and mitochondrial respiration markers.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF2 overexpression has also been shown to cause metabolic reprogramming in breast cancer.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	As expected, we also that IGF2 mediated the glycolysis in GISTs by targeting IGF1R signaling.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Increased expression of IGF2 is a common occurrence in various cancers and has been associated with increased resistance to chemotherapy, leading to a poorer prognosis.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Regarding GISTs, the standard first-line therapeutic approach involves the use of imatinib.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Imatinib, a potent TKI, is the primary treatment for GISTs, and significantly contributes to the progression-free survival of GIST patients.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Our investigation revealed a noteworthy correlation of increased IGF2 expression with the induction of GISTs resistance to imatinib concurrently with a reduction of imatinib-induced apoptosis in GIST cells.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	These findings underscore IGF2 as a potential regulator of GISTs imatinib resistance, and a promising target for interventions aimed at reversing such resistance.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Intriguingly, our study further showed that IGF2 regulates cellular sensitivity to imatinib by modulating glycolysis.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	The study had some limitations of this study.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	First, except for GIST cells, the role of IGF2 on GIST patient samples needs verification.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Even though we found that IGF-2 overexpression increased the resistance of GIST cells to imatinib in cell culture, the clinical effect needs to be verified.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Secondly, our results allows speculation that IGF2 was involved in the resistance to chemotherapy and a worse GISTs prognosis.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	However, the molecular mechanism of IGF2 specific to GISTs requires further investigation.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	We will consider these issues in future studies.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	In addition, studies have found that hypoglycemia in patients with non-islet cell tumor-induced GISTs may be aggravated by imatinib.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	A recent case study reported that a GISTs that produced big-IGF2 also caused severe hypoglycemia.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	We also hope to investigate that in future experiments.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	This study investigated IGF2 regulation of metastasis and imatinib resistance in GISTs.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	IGF2 interacted with IGF1R to regulate glycolysis.
PMC11334037	Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors	Our results found that IGF2 targeting of IGF1R signaling improved metastasis and imatinib chemosensitivity via driving glycolysis in GISTs and support potential use of IGF2 to reverse imatinib resistance in GISTs patients.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	•LARP7 highly expressed in GIST tumors comparing to peri‑tumors at both mRNA and protein levels.•LARP7 highly expression in small intestine GISTs was associated with poor prognostic.•LARP7 highly expression had relationship with imatinib drug-resistance.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	LARP7 highly expressed in GIST tumors comparing to peri‑tumors 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	LARP7 highly expression in small intestine GISTs was associated with poor prognostic.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	LARP7 highly expression had relationship with imatinib drug-resistance.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	They primarily originated from precursor cells of the interstitial cells of Cajal.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GISTs predominantly occur in the stomach (60–65 %), and the small intestine (20–25 %), with a small fraction in the colorectum, esophagus, and other locations.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Furthermore, the liver is the most common site for metastatic relapse.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GISTs can develop across all age groups; no significant gender preference has been observed.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Mutations in KIT or PDGFRA serve as mutually exclusive drivers of tumorigenesis in the majority of GISTs .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Specifically, mutations in KIT (exons 11, 9, and 13) or PDGFRA (exons 18, 14, and 12) maintain these tyrosine kinases in an active conformation, leading to prolonged activation of downstream kinases in the MEK-MAPK and PI3 K pathways.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Benefiting from these mutation findings, the introduction of tyrosine kinase inhibitors (TKIs), notably imatinib, has significantly improved the survival of GIST patients who were previously resistant to standard cytotoxic treatments, extending their survival from 18 months to over five years .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	However, acquired mutations in KIT or PDGFRA can confer resistance to imatinib and other TKI therapies.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Besides, tumor size, location, and mitotic count are assessed as risk factors for GIST .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	In recent years, significant progress has been made in research related to the pathogenesis of GIST, mainly due to advancements in sequencing technologies.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Through integrating genomic mutations and gene expression profiles, Keiichi et al. found that genes in the PI3 K and cell cycle pathways tended to be aberrantly expressed, resulting in the malignant progression of GIST .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Guo et al. conducted a transcriptomic study of GIST with liver metastasis and revealed that genes regulating epithelial-mesenchymal transition were abnormally expressed, promoting the metastasis process .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Several long non-coding RNAs (lncRNAs) and microRNAs have also been found to be closely associated with the pathogenesis and drug resistance of GIST.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Since 2018, Hemming et al. have published a series of influential studies highlighting the crucial roles of transcription factors and chromatin regulators in GIST pathophysiology [, , ], including HAND1, BARX1 , GPR20 , MOZ, Menin-MLL , and CDK2 .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	A quantitative proteomics and phosphoproteomics analysis of a GIST cohort identified four clinically relevant subgroups and provided a valuable data resource .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Despite these numerous achievements, the molecular mechanisms underlying tumorigenesis, development, and resistance to TKIs still need to be fully elucidated.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	In this study, we collected transcriptomic and proteomic datasets to identify genes that play critical roles in the occurrence and development of GIST, aiming to assist in the formulation of more precise treatment strategies.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Eight transcriptome datasets, including those for GIST and normal tissue (Table 1), were downloaded from the Gene Expression Omnibus (GEO), a public repository of high-throughput gene expression data.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GSE155800 (mRNA) and GSE225819 were analyzed to identify critical genes associated with GIST.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GSE112, which contains survival information, was employed to validate the results related to survival.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GSE17743 and GSE136755 were included to explore the expression distribution of essential genes across different clinical characteristic groups.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GSE89051 (miRNA) and GSE155800 (lncRNA) were utilized to validate the predicted lncRNAs and miRNAs in the regulatory network.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GSE132542 and GSE51697, which contain information on imatinib resistance, were downloaded to assess the expression of the key gene.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Table 1GIST transcriptome datasets.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Table 1GEO_IDChipSample_typeSample_numberPaper/Contributor(s)GSE155800Illumina HiSeq 3000 (Homo sapiens)GIST (Imatinib-sensitive and resistant) and normal samplesTumor (n = 10) Non-Tumor (n = 10)PMID: 34,458,010GSE225819Affymetrix Human Gene Expression Array (GPL15207)GIST samples (with liver metastistic) and paired samplesTumor (n = 20) Non-tumor (n = 20)PMID: 36,911,388GSE112Human Unigene I, part 1 (GPL9); Human Unigene I, part 2 (GPL10)GIST samples with survival informationTumor (n = 16)Bergmann F et al.GSE17743[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 ArrayGIST samples with clinical informationTumor (n = 29)PMID: 19,943,934GSE136755Agilent-039,494 SurePrint G3 Human GE v2 8 × 60 K Microarray 039,381 (Probe Name version)GIST samplesPrimary tumor (n = 59)PMID: 31,553,483GSE89051Illumina HiSeq 2500 (Homo sapiens)GIST and paired samplesTumor (n = 15) Non-Tumor (n = 15)PMID: 30,557,328GSE132542[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 ArrayGIST samples (imatinib-naïve and imatinib-resistant)imatinib-naïve (n = 14) imatinib-resistant (n = 15)PMID: 31,238,586GSE51697[HG-U133A_2] Affymetrix Human Genome U133A 2.0 ArrayTAMs isolated from GISTs (untreated, responding to imatinib (sensitive), or resistant to imatinib (resistant))untreated (n = 12), sensitive (n = 5), and resistant (n = 4)PMID: 24,323,358 GIST transcriptome datasets.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The proteomic data for GIST, encompassing both imatinib-sensitive and imatinib-resistant samples, were obtained from the notable study by Sun et al. .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Survival analysis data were utilized for the initial screening of genes.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Additionally, proteomic data from a previous study by Liu et al. were downloaded to validate the expression trends of the key gene.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Differential expression analysis of the high-throughput sequencing dataset GSE155800 was conducted using DESeq2 (version 1.42.0).
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The array datasets GSE225819, GSE89051, GSE132542, and GSE51697 were analyzed using limma (version 3.58.1).
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	A filtering criterion of \|log2(fold change)\| > 1 and p < 0.05 was applied to identify significantly differentially expressed genes.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Additionally, differentially expressed proteins were directly obtained from the study conducted by Sun et al. Functional enrichment analysis was performed using the Cytoscape (version 3.10.1) plugin GlueGO (version 2.5.10) for genes exhibiting significant differential expression at both the mRNA and protein levels with consistent trends.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Up-regulated and down-regulated gene sets were analyzed separately for the enrichment of Gene Ontology (GO) terms, including GO_BiologicalProcess (GO_BP), GO_CellularComponent (GO_CC), GO_MolecularFunction (GO_MF), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and REACTOME pathways and reactions.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GO terms were filtered to eliminate redundancy.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	All enrichment results were subjected to a significance threshold of p < 0.05.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The Cytoscape plugin yFiles Layout Algorithms was employed to visualize significantly enriched pathways.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	For survival analysis, we utilized the protein expression and prognosis data (overall survival (OS) time and progress-free survival (PFS) time) from the study conducted by Sun et al. Univariate Cox regression and Kaplan-Meier analysis were performed using the survival (version 3.5–7) and survminer (version 0.4.9) packages.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The forestplot package (version 3.1.3) was utilized to visualize the results of the univariate COX regression.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The transcriptome data of GSE225819 and GSE136755 were analyzed using TIMER2.0 to determine the infiltration proportions of various immune cells in the immune microenvironment.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The results from TIMER, CIBERSORT, CIBERSORT-ABS, xCell, and MCP-counter were subsequently compared between high-and low-expression groups.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Pearson correlation coefficients were also calculated to assess the relationship between gene expression and immune cell infiltration proportions.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	CytoSig is a computational method designed to aid immunologists in predicting the activity of 43 cytokine signaling pathways in biological samples based on gene expression profiles .
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	In this study, we utilized CytoSig to assess the activation levels of cytokine pathways in the GSE225819 and GSE136755 datasets, correlating these levels with LARP7 expression.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The Encyclopedia of RNA Interactomes (ENCORI) database provides a comprehensive resource about the RNA interactome, including RNA-RNA, RNA-protein, and RNA-miRNA interactions.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Leveraging the ENCORI database, we identified miRNAs that target LARP7, lncRNAs target hsa-miR-138–5p, RNA-binding proteins (RBPs) that interact with LARP7 mRNA, and RNAs that are targeted by the LARP7 protein.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The miRNAs and lncRNAs were validated using transcriptomic data from GSE85091 and GSE155800.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The transcriptome datasets GSE132542 and GSE51697, which include untreated, imatinib-sensitive, and imatinib-resistant GIST patients, were utilized to identify drug resistance-related genes and to illustrate the expression differences of LARP7 between resistant and sensitive patients.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Additionally, proteomic data from Sun et al.’s study were incorporated into the analysis.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	To further explore potential drugs that could benefit GIST patients exhibiting high LARP7 expression, we utilized the oncoPredict package (version 0.2) to predict IC50 values for the GSE225819 and GSE136755 datasets based on the results of 198 drugs tested on 805 cancer cell lines in the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) database.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	We subsequently identified drugs with significantly lower predicted IC50 values in the high LARP7 expression group.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Following identifying a significant negative correlation between LARP7 expression and predicted IC50 values, we selected potential drugs that may benefit GIST patients.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	GIST and adjacent non-cancerous tissues were collected from four patients diagnosed with GIST at the Sichuan Provincial People's Hospital, Sichuan, China.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	These samples were promptly frozen, stored in liquid nitrogen, and maintained at −80 °C for subsequent analysis.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The study protocol was granted approval by the Ethics Committee of Sichuan Provincial People's Hospital (Approval Number: 2024–226), adhering to the principles of the Declaration of Helsinki.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	Each patient provided written informed consent and approved the utilization of their tissues for research purposes.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The GIST-T1 cell line (Cat.:
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	, established from the stomach tumor of a 47-year-old Japanese woman with metastatic complex GIST, was obtained from Cellverse Bioscience Technology Co., Ltd. (Shanghai, China) and was Short Tandem Repeat (STR) identified.
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	The GIST-882 cell line (Cat.:
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	, derived from a female patient with GIST who harbored a homozygous missense mutation in KIT exon 13, was purchased from Qingqi (Shanghai) Biotechnology Development Co., Ltd. (Shanghai, China).
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	These cells were cultured in Dulbecco's Modified Eagle Medium (DMEM, Cat.:
PMC11867541	Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors	PM150210, Wuhan Pricella Biotechnology Co., Ltd., Wuhan, China) with 10 % fetal bovine serum (FBS, Cat.:
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) and 1 % penicillin-streptomycin (Cat.:

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

We explored the mechanism of IGF2 in imatinib resistance in GISTs and whether IGF2 enhanced metastasis and imatinib resistance by driving glycolysis by targeting IGF1R signaling transduction.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF2, identified as an imprinted gene, exhibits a significant impact on cancer progression when its imprinting is lost or relaxed, leading to heightened autocrine IGF2 levels and increased secretion in malignant cells.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Numerous studies have revealed the upregulation of IGF2 in various cancers such as hepatocellular carcinoma, correlating with resistance to chemotherapy and a poorer prognosis[12-14].

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Our investigation, which focused on DEGs associated with liver metastasis and drug resistance in GISTs, we observed elevated levels of IGF2 in GISTs cases linked to liver metastasis and drug resistance.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Our comprehensive analysis included assessment of cell proliferation, viability, migration, and invasiveness.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

The findings strongly suggest that overexpression of IGF2 induce the proliferation, metastasis, and EMT of GIST cells.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF1R, is a tyrosine kinase receptor that can be triggered by IGF2 and has a pivotal role in regulating mammalian development, metabolism, and growth.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF1R is known to be upregulated in various human solid tumors.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Its involvement in cell promoting cell proliferation and inhibiting programmed cell death is facilitated by activation of its tyrosine kinase and the subsequent engagement of the Ras/Raf/MEK and PI3K/AKT/mTOR signaling pathways.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

The IGF2-IGF1R signaling axis assumes critical significance in governing cell proliferation, differentiation, EMT, migration, drug resistance, and maintaining stemness in malignancies.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

This investigation further demonstrated the activation of IGF1R signaling by IGF2 in GIST cells.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

It highlights the role of IGF2 as a pivotal chromatin factor that controls the expression level of IGF1R and modulates downstream signaling by the PI3K/AKT pathway.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF2 also upregulated the expression of glycolytic and mitochondrial respiration markers.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF2 overexpression has also been shown to cause metabolic reprogramming in breast cancer.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

As expected, we also that IGF2 mediated the glycolysis in GISTs by targeting IGF1R signaling.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Increased expression of IGF2 is a common occurrence in various cancers and has been associated with increased resistance to chemotherapy, leading to a poorer prognosis.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Regarding GISTs, the standard first-line therapeutic approach involves the use of imatinib.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Imatinib, a potent TKI, is the primary treatment for GISTs, and significantly contributes to the progression-free survival of GIST patients.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Our investigation revealed a noteworthy correlation of increased IGF2 expression with the induction of GISTs resistance to imatinib concurrently with a reduction of imatinib-induced apoptosis in GIST cells.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

These findings underscore IGF2 as a potential regulator of GISTs imatinib resistance, and a promising target for interventions aimed at reversing such resistance.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Intriguingly, our study further showed that IGF2 regulates cellular sensitivity to imatinib by modulating glycolysis.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

The study had some limitations of this study.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

First, except for GIST cells, the role of IGF2 on GIST patient samples needs verification.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Even though we found that IGF-2 overexpression increased the resistance of GIST cells to imatinib in cell culture, the clinical effect needs to be verified.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Secondly, our results allows speculation that IGF2 was involved in the resistance to chemotherapy and a worse GISTs prognosis.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

However, the molecular mechanism of IGF2 specific to GISTs requires further investigation.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

We will consider these issues in future studies.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

In addition, studies have found that hypoglycemia in patients with non-islet cell tumor-induced GISTs may be aggravated by imatinib.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

A recent case study reported that a GISTs that produced big-IGF2 also caused severe hypoglycemia.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

We also hope to investigate that in future experiments.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

This study investigated IGF2 regulation of metastasis and imatinib resistance in GISTs.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

IGF2 interacted with IGF1R to regulate glycolysis.

PMC11334037

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

Our results found that IGF2 targeting of IGF1R signaling improved metastasis and imatinib chemosensitivity via driving glycolysis in GISTs and support potential use of IGF2 to reverse imatinib resistance in GISTs patients.

PMC11867541