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A Pipeline to Call Multilevel Expression Changes between Cancer and Normal Tissues and Its Applications in
Wei Gao1, Jianwei Yang1, Changhua Zhuo2
1Departments of Internal Medicine-Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, China.
Abstract:
Differential gene analyses on gastric cancer usually focus on expression change of single genes between tumor and adjacent normal tissues. However, besides changes on single genes, there are also coexpression and expression network module changes during the development of gastric cancer. In this study, we proposed a pipeline to investigate various levels of changes between gastric cancer and adjacent normal tissues, which were used to repurpose potential drugs for treating gastric cancer. Specifically, we performed a series of analyses on 242 gastric cancer samples (33-normal, 209-cancer) downloaded from the cancer genome atlas (TCGA), including data quality control, differential gene analysis, gene coexpression network analysis, module function enrichment analysis, differential coexpression analysis, differential pathway analysis, and screening of potential therapeutic drugs. In the end, we discovered some genes and pathways that are significantly different between cancer and adjacent normal tissues (such as the interleukin-4 and interleukin-13 signaling pathway) and screened perturbed genes by 2703 drugs that have a high overlap with the identified differentially expressed genes. Our pipeline might be useful for understanding cancer pathogenesis as well as gastric cancer treatment.
Insights
This study introduces a new pipeline to analyze gastric cancer by examining gene expression changes and networks. It identifies key genes and pathways, aiding in understanding cancer development and finding new drug treatments.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Gastric cancer research often focuses on single gene expression changes.
- Gene coexpression and network alterations are also crucial in gastric cancer development.
Purpose of the Study:
- To develop a comprehensive pipeline for analyzing gastric cancer at multiple molecular levels.
- To identify potential drug repurposing candidates for gastric cancer treatment.
Main Methods:
- Utilized a dataset of 242 gastric cancer samples from The Cancer Genome Atlas (TCGA).
- Performed differential gene expression, gene coexpression network analysis, and differential pathway analysis.
- Screened 2703 drugs for potential therapeutic applications based on identified gene perturbations.
Main Results:
- Identified significant differences in gene expression and pathways between gastric tumors and adjacent normal tissues.
- Highlighted the interleukin-4 and interleukin-13 signaling pathway as notably altered.
- Found a substantial overlap between perturbed genes and drug targets.
Conclusions:
- The developed pipeline offers a multi-level approach to understanding gastric cancer.
- This method can aid in discovering novel therapeutic strategies and drug repurposing for gastric cancer.
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