Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2020; 26(8): 789-803
Published online Feb 28, 2020. doi: 10.3748/wjg.v26.i8.789
Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma
Long Pan, Jing Fang, Ming-Yu Chen, Shu-Ting Zhai, Bin Zhang, Zhi-Yu Jiang, Sarun Juengpanich, Yi-Fan Wang, Xiu-Jun Cai
Long Pan, Jing Fang, Ming-Yu Chen, Shu-Ting Zhai, Bin Zhang, Zhi-Yu Jiang, Sarun Juengpanich, Yi-Fan Wang, Xiu-Jun Cai, Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
Long Pan, Jing Fang, Ming-Yu Chen, Shu-Ting Zhai, Bin Zhang, Yi-Fan Wang, Xiu-Jun Cai, Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310016, Zhejiang Province, China
Author contributions: All authors designed the research; Zhai ST, Zhang B, and Jiang ZY collected the data; Pan L and Fang J performed the statistical analysis and wrote the paper; Chen MY, Juengpanich S, Wang YF, and Cai XJ revised the paper.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Sir Run Run Shaw Hospital.
Conflict-of-interest statement: All the authors declare no conflicts of interest related to this article.
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: Xiu-Jun Cai, MD, PhD, FACS, FRCS, Professor, Surgeon, Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Jianggan District, Hangzhou 310016, Zhejiang Province, China. srrsh_cxj@zju.edu.cn
Received: October 3, 2019
Peer-review started: October 3, 2019
First decision: November 10, 2019
Revised: December 20, 2019
Accepted: February 12, 2020
Article in press: February 12, 2020
Published online: February 28, 2020
Abstract
BACKGROUND

Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed.

AIM

To identify potential key genes associated with tumor microenvironments and the prognosis of HCC.

METHODS

The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model.

RESULTS

HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (STSL2, TMC5, DOK5, RASGRP2, NLRC3, KLRB1, CD5L, CFHR3, ADH1C, and UGT2B15) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival.

CONCLUSION

This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.

Keywords: Hepatocellular carcinoma, Tumor microenvironment, Differentially expressed genes, Overall survival

Core tip: We performed an integrated bioinformatics analysis to assess the influence of tumor microenvironment on the prognosis of patients with hepatocellular carcinoma (HCC). The results found that HCC patients with a high immune/stromal infiltration level had better survival benefits than patients with a low infiltration level. Ten microenvironment-related key genes were screened and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival. Our study provided novel insight into the potential association of tumor microenvironment with HCC prognosis and molecular targeted therapy of HCC in the future.