Research Paper Volume 12, Issue 17 pp 17418—17435
Identification of subtype-specific genes signature by WGCNA for prognostic prediction in diffuse type gastric cancer
- 1 Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
Received: April 6, 2020 Accepted: July 7, 2020 Published: September 11, 2020
https://doi.org/10.18632/aging.103743How to Cite
Abstract
Background: Gastric cancer is a common malignancy and had poor response to treatment due to its strong heterogeneity. This study aimed to identify essential genes associated with diffuse type gastric cancer and construct a powerful prognostic model.
Results: We conducted a weighted gene co-expression network analysis (WGCN) using transcripts per million (TPM) expression data from The Cancer Genome Atlas (TCGA) to find out the module related with diffuse type gastric cancer. Combining Least Absolute Shrinkage and Selection Operator (LASSO) with multi-cox regression, the 10 specific genes risk score model of diffuse type gastric cancer was established. The concordance index (0.97), the area under the respective ROC curves (AUCs) (1-years: 0.98; 3-years: 1; 5-years: 1) and survival difference of high- and low risk groups (p=2.84e-10) of this model in TCGA dataset were obtained. The moderate predicting performance was observed in the independent cohort of GSE15459 and GSE62254. The results of the gene set enrichment analysis (GSEA) using high-and low risk group as phenotype indicated differential expression of tumor-related pathways.
Conclusion: Thus, we constructed a reliable prognostic model for diffuse type gastric cancer, which should be beneficial for clinical therapeutic decision-making.
Abbreviations
GC: gastric cancer; WHO: World Health Organization; TCGA: The Cancer Genome Atlas; WGCNA: weighted gene co-expression network analysis; TPM: transcripts per million; FPKM: per million mapped reads; GEO: Gene Expression Omnibus; MEs: module eigengenes; LASSO: Least Absolute Shrinkage and Selection Operator; ROC: receiver operating characteristic; AUC: the area under the respective ROC curves; OS: overall survival; GSEA: the gene set enrichment analysis; HCM: hypertrophic cardiomyopathy; C-index: The concordance index; CAMs: cell adhesion molecules; htlv-1: human T-cell lymphotropic virus type I; EB: Epstein-Barr virus.