Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5266-5282
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5266
Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma
Qi-Feng Chen, Wang Li, Pei-Hong Wu, Lu-Jun Shen, Zi-Lin Huang
Qi-Feng Chen, Wang Li, Pei-Hong Wu, Lu-Jun Shen, Zi-Lin Huang, Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China
Author contributions: Chen QF, Huang ZL, and Li W contributed to study conceptualization; Chen LJ contributed to the methodology; Wu PH provided software; Chen QF, Wu PH, and Huang ZL performed the validation; Chen QF, Wu PH, Huang ZL, and Shen LJ analyzed the data; Chen QF and Li W prepared the original draft; Chen QF, Wu PH, Huang ZL, and Shen LJ reviewed and edited the manuscript; Chen QF contributed to data visualization; Huang ZL supervised the study.
Supported by the National Natural Science Foundation of China, No. 81801804.
Conflict-of-interest statement: The authors deny any conflict of interest.
Data sharing statement: The data used in this manuscript are accessible through https://portal.gdc.cancer.gov/.
ARRIVE guidelines statement: The ARRIVE guidelines have been adopted.
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/
Corresponding author: Zi-Lin Huang, MD, Professor, Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; 651 Dongfeng Road East, Yuexiu District, Guangzhou 510060, Guangdong Province, China. huangzl@sysucc.org.cn.
Telephone: +86-20-87343272 Fax: +86-20-87343392
Received: April 22, 2019
Peer-review started: April 22, 2019
First decision: June 10, 2019
Revised: July 18, 2019
Accepted: August 7, 2019
Article in press: June 10, 2019
Published online: September 21, 2019
Processing time: 153 Days and 18.8 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is a common subtype of liver cancer, which has become a serious health threat worldwide. Hepatitis B virus (HBV) has been identified as a leading cause of HCC. Increasing evidence indicates that cancer immune infiltration is associated with clinical outcomes. However, no credible prognosis signature for HBV-associated HCC has been constructed through systemically assessing bulk tumor transcriptomic immune landscape.

Research motivation

Tumor-infiltrating immunocytes represent a vital prognosis clue in HBV-associated HCC patients. In this study, a new immune model for HBV-associated HCC cases was developed through systematically assessing the bulk tumor transcriptomic immune landscape.

Research objectives

The current research aimed to establish a prognosis-related immune signature based on bulk tumor transcriptome-derived immune infiltrate compositions, thus improving the prognosis prediction accuracy for HBV-associated HCC.

Research methods

The fractions of 22 immunocyte types extracted based on public datasets were predicated using the cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Furthermore, an immunoscore was calculated based on immunocyte type fractions by the least absolute shrinkage and selection operator (LASSO) model.

Research results

The immunoscore constituted by eight immunocyte type fractions was constructed by adopting the LASSO model, which displayed a high sensitivity and specificity for overall survival (OS), and the areas under the curves for the 1-year, 3-year, and 5-year OS were 0.971, 0.912, and 0.975, respectively. Difference in OS between the low-immunoscore and high-immunoscore groups was statistically significant. Additionally, a nomogram was established to expand the applied range of the model, which included the immunoscore as well as other clinical characteristics. The related pathways were enriched through gene set enrichment analysis.

Research conclusions

The established immunoscore showed high prognosis prediction accuracy for patients with HBV-associated HCC, which may facilitate the risk stratification and provide valuable clinical suggestions for individual cases.

Research perspectives

Findings of this study suggested that the tumor-infiltrating immunocytes could be used as promising biomarkers to predict the prognosis for HBV-associated HCC patients. This forms the framework for identification of efficient prognosis predictors and molecular biomarkers for HCC patients in the future.