Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma

doi:10.3748/wjg.v26.i8.789

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Feb 28, 2020 (publication date) through Mar 5, 2026

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World Journal of Gastroenterology

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1007-9327

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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.

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
Processing time: 147 Days and 18.3 Hours

ARTICLE HIGHLIGHTS

Research background

Tumor microenvironments (TMEs) play an important role in cancer development, including hepatocellular carcinoma (HCC), hence affecting clinical outcomes. Stromal and immune cells are two major components of nontumor cells in TMEs and are considered to be valuable for the prognostic evaluation of tumors. Nonetheless, the infiltration level of stromal/immune cells and specific roles of TME-related genes in HCC have not yet been clarified.

Research motivation

More biomarkers are required for the diagnosis and treatment of HCC.

Research objectives

The present study investigated potential key genes associated with tumor microenvironments and the prognosis of HCC.

Research methods

The ESTIMATE method was used to predict the infiltration levels of stromal and immune cells in HCC. Differentially expressed genes (DEGs) between patients with high and low infiltration levels were screened using the TCGA database and linked to overall survival of HCC. DEGs were verified by four other independent HCC cohorts and further selected by LASSO Cox regression analysis.

Research results

HCC patients with high immune/stromal infiltration levels had better survival benefits than patients with low infiltration levels. A total of 147 DEGs were identified to be associated with overall survival. Moreover, 52 survival-related DEGs were validated, and ten key genes were selected by LASSO algorithm, which were further used to construct a prognostic classifier, showing a good performance in predicting overall survival.

Research conclusions

Our study screened a series of TME-related genes and provided a novel insight into the potential association of TME with HCC prognosis and molecular targeted therapy of HCC in the future.

Research perspectives

HCC and TMEs are an integral whole. More in-depth research should be conducted to reveal the important role of components of TMEs in HCC to develop novel anti-cancer treatments via targeting TME-related cells and the extracellular matrix.