Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2018; 24(43): 4906-4919
Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4906
Prognostic value of sorting nexin 10 weak expression in stomach adenocarcinoma revealed by weighted gene co-expression network analysis
Jun Zhang, Yue Wu, Hao-Yi Jin, Shuai Guo, Zhe Dong, Zhi-Chao Zheng, Yue Wang, Yan Zhao
Jun Zhang, Shuai Guo, Zhe Dong, Zhi-Chao Zheng, Yue Wang, Yan Zhao, Department of Gastric Cancer, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), Shenyang 110042, Liaoning Province, China
Yue Wu, Department of Emergency, Sheng Jing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
Hao-Yi Jin, Pancreatic and Thyroid Surgery Department, Sheng Jing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
Author contributions: Zhang J performed the majority of experiments and analyzed the data and drafted the manuscript; Zheng ZC, Zhao Y designed the research; Wu Y, Dong Z conducted the immunohistochemistry assays and assisted in writing the manuscript; Guo S, Wang Y collected and analyzed the data; Zhao Y provided critical revision of the manuscript for important intellectual content; Jin HY provided critical revision of the manuscript for important intellectual content.
Supported by Liaoning S&T Project, No. 2015020269.
Institutional review board statement: The study was reviewed and approved by the Faculty of Science Ethics Committee at Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University) (20150308-2).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yan Zhao, PhD, Professor, Vice-President, Department of Gastric Cancer, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. zhaoyan@cancerhosp-ln-cmu.com
Telephone: +86-24-31916823 Fax: +86-24-24315679
Received: August 2, 2018
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
Abstract
AIM

To detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma (SA) prognosis.

METHODS

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.

RESULTS

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].

CONCLUSION

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.

Keywords: Stomach adenocarcinoma, The Cancer Genome Atlas, Weighted gene co-expression network analysis, Sorting nexin 10, Clinicopathological predictors, Disease-free survival, Overall survival

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.