Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4906
Peer-review started: August 2, 2018
First decision: October 5, 2018
Revised: October 17, 2018
Accepted: October 21, 2018
Article in press: October 21, 2018
Published online: November 21, 2018
Processing time: 111 Days and 22.9 Hours
To detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma (SA) prognosis.
The Cancer Genome Atlas database was used to obtain RNA sequences as well as complete clinical data of SA and adjacent normal tissues from patients. Weighted gene co-expression network analysis (WGCNA) was used to investigate the meaningful module along with hub genes. Expression of hub genes was analyzed in 362 paraffin-embedded SA biopsy tissues by immunohistochemical staining. Patients were classified into two groups (according to expression of hub genes): Weak expression and over-expression groups. Correlation of biomarkers with clinicopathological factors indicated patient survival.
Whole genome expression level screening identified 6,231 differentially expressed genes. Twenty-four co-expressed gene modules were identified using WGCNA. Pearson’s correlation analysis showed that the tan module was the most relevant to tumor stage (r = 0.24, P = 7 × 10-6). In addition, we detected sorting nexin (SNX)10 as the hub gene of the tan module. SNX10 expression was linked to T category (P = 0.042, χ2 = 8.708), N category (P = 0.000, χ2 = 18.778), TNM stage (P = 0.001, χ2 = 16.744) as well as tumor differentiation (P = 0.000, χ2 = 251.930). Patients with high SNX10 expression tended to have longer disease-free survival (DFS; 44.97 mo vs 33.85 mo, P = 0.000) as well as overall survival (OS; 49.95 vs 40.84 mo, P = 0.000) in univariate analysis. Multivariate analysis showed that dismal prognosis could be precisely predicted clinicopathologically using SNX10 [DFS: P = 0.014, hazard ratio (HR) = 0.698, 95% confidence interval (CI): 0.524-0.930, OS: P = 0.017, HR = 0.704, 95%CI: 0.528-0.940].
This study provides a new technique for screening prognostic biomarkers of SA. Weak expression of SNX10 is linked to poor prognosis, and is a suitable prognostic biomarker of SA.
Core tip: This study used The Cancer Genome Atlas (TCGA) and clinical data to identify sorting nexin (SNX)10 as associated with poor prognosis in stomach adenocarcinoma (SA). Firstly, we downloaded the TCGA-STAD RNA-seq data through R and identified the differentially expressed genes. Weighted gene co-expression network analysis was used to clarify the connection between modules and clinical information. We then chose SNX10 as the hub-gene of the tan-module after considering module membership, genes with high gene significance, degree and Molecular Complex Detection scores. Our center’s SA data were used to evaluate our hypothesis. Our findings demonstrated that weak expression of SNX10 is linked to poor SA prognosis.