Dataset Information

Driver Gene Alterations in Malignant Progression of Gastric Cancer.

ABSTRACT: The identification of driver genes is of great importance in modern medical research. It is also an essential factor in the development of individualization and has a positive effect on understanding the causes of cancer. Gene mutations are the primary cause of the outcomes of the process of tumorigenesis. Driver genes can be used as therapeutic targets for tumor-specific mutation-dependent overexpression. This study sought to identify mutation-based driver genes in gastric cancer (GC) by applying comprehensive gene expression and copy number analysis. Multiplatform analysis was used to identify four major genomic subtypes of GC. The most prominent cancer-related variations observed in this cohort were TTN mutations (found in 56% of tumors), followed by TP53 (51%), MUC16 (7%), and LRP1B (6%) mutations. In our analysis, mutation characteristics were mainly related to the DNA mismatch repair system. In addition, 34 candidate driver oncogenes were identified in GC. Further research identified six GC-related driver genes associated with the levels of immune infiltration of different immune cells and the majority of immune markers. Our mutation-based study of driver oncogenes identified potential drug targets in GC.

SUBMITTER: Dong Y

PROVIDER: S-EPMC9315095 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Driver Gene Alterations in Malignant Progression of Gastric Cancer.

Dong Yuanqiang Y Song Ning N Wang Jun J Shi Liubin L Zhang Ziqiang Z Du Jianjun J

Frontiers in oncology 20220712

The identification of driver genes is of great importance in modern medical research. It is also an essential factor in the development of individualization and has a positive effect on understanding the causes of cancer. Gene mutations are the primary cause of the outcomes of the process of tumorigenesis. Driver genes can be used as therapeutic targets for tumor-specific mutation-dependent overexpression. This study sought to identify mutation-based driver genes in gastric cancer (GC) by applyi ...[more]

PMID: 35903675

Similar Datasets

Project description:Background: Cancer-associated fibroblasts (CAFs) are principal constituents of the tumor microenvironment (TME) and play a critical role in tumor progression. The CXCL12/CXCR4 axis regulates multiple facets of the TME. The aim of this study was to determine the relationship between CXCL12 expression in CAFs and the malignant progression of gastric cancer (GC). Methods: In the GEO (Gene Expression Omnibus) database, we performed transcriptome analysis on paired gastric cancer RNA sequencing samples, and scRNA analysis was performed on advanced malignant GC samples from the scRNA sequencing data set. Fibroblast cells were co-cultured with GC cells, and invasion, migration, epithelial-mesenchymal transformation (EMT) were determined. After blocking the expression of fibroblast CXCL12, cells were co-cultured with a GC cell line. Detection of GC cell line invasion, migration, EMT and CXCR4, Wnt5a and β-Catenin expression levels was performed. Primary CAFs and gastric normal fibroblasts were isolated and CXCL12 mRNA and protein expression were determined. In addition, a cohort of 285 GC cases was established, protein expression was evaluated immunohistochemically, and prognostic results were analyzed. Results: GC transcriptome analysis suggested that cytokine-cytokine receptor interaction and the Wnt signaling pathway in GC tissues were significantly up-regulated. scRNA analysis of advanced malignant GC samples showed that severe intestinal metaplasia (SIM) in GC specimens of different malignant grades had obvious fibroblast clusters compared to non-atrophic gastritis (NAG) and early gastric cancer (EGC). In the SIM group, fibroblast cluster, CXCL12, CXCR4, and Wnt5a were overexpressed. Co-culturing with fibroblast cells significantly increased the invasion, migration, and EMT of GC cells, and blocking CXCL12 in CAFs disturbed the expression of Wnt5a and β-catenin. In our cohort of GC patients, high CXCL12 expression in CAFs significantly correlated with histological grade (P = 0.012) and TNM stage (P = 0.014), as well as with poor overall survival (p = 0.0107). Conclusion: High expression of CXCL12 in CAFs in a GC microenvironment can affect the migration, invasion, and EMT of GC cells. Furthermore, it can cause poor prognosis in patients with GC.

Dataset Information

Driver Gene Alterations in Malignant Progression of Gastric Cancer.

Publications

Driver Gene Alterations in Malignant Progression of Gastric Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets