Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1412-1423
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1412
Expression patterns of cluster of differentiation 147 impact the prognosis of hepatocellular carcinoma
Yun-Ji Xu, Hong-Jie He, Peng Wu, Wen-Bing Li
Yun-Ji Xu, Hong-Jie He, Peng Wu, Wen-Bing Li, Department of General Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
Author contributions: Xu YJ was responsible for analyzing the data and composing the manuscript; He HJ and Wu P contributed to acquiring and analyzing data and reviewing the manuscript; Li WB contributed to conceiving and designing the present study; All authors read and approved the final manuscript and confirmed the authenticity of all the raw data.
Institutional review board statement: This study was approved by the Second Clinical College Committee of South China University.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: The data of this study are available upon reasonable request through the corresponding author at loverpig520@163.com.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Bing Li, PhD, Doctor, Department of General Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, No. 28 Changsheng West Road, Hengyang 421001, Hunan Province, China. loverpig520@163.com
Received: March 28, 2023
Peer-review started: March 28, 2023
First decision: May 17, 2023
Revised: May 30, 2023
Accepted: June 27, 2023
Article in press: June 27, 2023
Published online: August 15, 2023
Processing time: 135 Days and 4.8 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) has very low overall survival. According to global cancer statistics, approximately 905677 new cases were reported in 2020, with at least 830180 of them being fatal. Cluster of differentiation 147 (CD147) is a novel, transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development. Based on the reports described previously, we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC. To study this possibility, expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed, and a hazard ratio (HR) was established.

AIM

To explore the pattern of CD147 expression and its applicability in the prognosis of HCC. To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics. To determine if CD147 can be a reliable biomarker in HCC prognosis.

METHODS

The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database. The expression patterns of CD147 were then validated by analyzing data from the GEO database. In addition, CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas. CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource. Accuracy, sensitivity, and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic (ROC) curves. Kaplan-Meier curves were plotted to estimate the HR of survival in HCC. Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed. Nomograms were used to establish probability points and predict prognosis.

RESULTS

Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC (P = 1.624 × 10-12 and P = 1.2 × 10-5, respectively). The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource (P < 0.05). Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival > 1 [log-rank test, P = 0.000542, HR (in high expression group): 1.856, 95% confidence interval (CI): 1.308 to 2.636]. ROC curves were plotted to analyze the 1-year, 3-year, and 5-year survival rates. The area under the ROC curve values were 0.675 (95%CI: 0.611 to 0.740), 0.623 (95%CI: 0.555 to 0.692), and 0.664 (95%CI: 0.582 to 9.745), respectively. Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences (univariate Cox, P = 0.00013, HR: 1.424, 95%CI: 1.884 to 1.707 and P = 0.00066, HR: 1.376, 95%CI: 1.145 to 1.654, respectively; multivariate Cox, P = 0.00578, HR: 1.507, 95%CI: 1.126 to 2.018 and P = 0.00336, HR: 1.443, 95%CI: 1.129 to 1.844, respectively). Nomograms were plotted to establish the probability points and predict prognosis. The total points ranged from 0 to 180, and the C-index value was 0.673 (95%CI: 0.600 to 1.000, P < 0.01).

CONCLUSION

Overexpression of CD147 was correlated with poor prognosis in HCC. The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC. CD147 can serve as a biomarker to predict the prognosis of HCC.

Keywords: Hepatocellular carcinoma; Cluster of differentiation 147; Prognosis; Clinical characteristics; Hazard ratio

Core Tip: Hepatocellular carcinoma (HCC) has very low overall survival. The discovery of a new biomarker related to prognosis would improve the prognosis of HCC. Cluster of differentiation 147 (CD147) is a novel transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development. In our study, we found that CD147 correlated with clinical characteristics and prognosis of HCC. Therefore, we suggest that CD147 can serve as a biomarker to predict the prognosis of HCC.