Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2020; 12(8): 857-876
Published online Aug 15, 2020. doi: 10.4251/wjgo.v12.i8.857
Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer
Xiang-Ting Qiu, Yu-Cui Song, Jian Liu, Zhen-Min Wang, Xing Niu, Jing He
Xiang-Ting Qiu, Jian Liu, Zhen-Min Wang, Department of Clinical Laboratory, Linyi Central Hospital, Linyi 276400, Shandong Province, China
Yu-Cui Song, Department of Operating Room, Linyi Central Hospital, Linyi 276400, Shandong Province, China
Xing Niu, Second Clinical College, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, Liaoning Province, China
Jing He, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
Author contributions: He J and Niu X conceived and designed the study; Qiu XT and Song YC conducted most of the experiments and data analyses, and wrote the manuscript; Liu J and Wang ZM participated in collecting the data and helped to draft the manuscript; all authors reviewed and approved the manuscript.
Conflict-of-interest statement: The authors declare that they no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Jing He, MD, PhD, Professor, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Guangzhou 510623, Guangdong Province, China. hejing198374@gmail.com
Received: February 10, 2020
Peer-review started: February 10, 2020
First decision: March 24, 2020
Revised: April 6, 2020
Accepted: June 17, 2020
Article in press: June 17, 2020
Published online: August 15, 2020
Abstract
BACKGROUND

Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC.

AIM

To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC.

METHODS

Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed.

RESULTS

Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3, and CTLA4). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients (P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration.

CONCLUSION

Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.

Keywords: Gastric cancer, Immune-related genes, Tumor microenvironment, Immune infiltration, Prognosis, Signature

Core tip: Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. Our study identified an immune-related prognostic signature for GC, which could accurately distinguish patients into high- and low- risk groups. High risk patients had a poorer prognosis. Multivariate Cox regression analysis demonstrated that the prognostic signature could independently predict GC prognosis. Furthermore, it was significantly associated with immune cell infiltration (especially macrophages). Therefore, the signature may possess prognostic value as a prediction tool for identification of patients who will benefit from immunotherapy.