Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2024; 16(8): 1131-1144
Published online Aug 27, 2024. doi: 10.4254/wjh.v16.i8.1131
Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma
Qiu-Ju Liang, Qin-Qin Long, Feng-Qin Tian, Qun-Ying Su, Xiao-Ying Zhu, Xi-Dai Long
Qiu-Ju Liang, Qin-Qin Long, Feng-Qin Tian, Qun-Ying Su, Xiao-Ying Zhu, Xi-Dai Long, Clinicopathological Diagnosis and Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Qiu-Ju Liang, Xi-Dai Long, Department of Tumor Pathology, Key Laboratory of Tumor Molecular Pathology of Guangxi Higher Education Institutes, Baise 533000, Guangxi Zhuang Autonomous Region, China
Co-first authors: Qiu-Ju Liang and Qin-Qin Long.
Author contributions: Liang QJ and Long QQ performed the experiments, formal analysis, and data curation, and they contributed equally to this work and should be considered as co-first authors; Tian FQ, Su QY, and Zhu XY constructed the histopathological sample library and collected the clinicopathological information and following-up data for all patients; Long XD conceptualized and designed the study, received grant support, had full access to the data, and is responsible for the integrity and accuracy of data analysis; all authors contributed to data acquisition and interpretation and reviewed and approved the final version.
Supported by the Science-Technology Planning Project of Guangxi, No. Guike-AD19245174; Guangxi Training Program for Medical High-level Academic Leaders, No. 6 of Guiweikejiaofa [2020]-15; Bose Talent Highland, No. 2020-3-2; Building Projects from the Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi, No. Guiweikejiaofa [2020]-17; the Key Laboratory of Tumor Molecular Pathology of Guangxi Colleges and Universities, No. Guijiaokeyan [2022]-10; and Clinical Key Specialty Building Project (For Pathology) of Guangxi, No. Guiweiyifa [2022]-21.
Institutional review board statement: The present study was approved by the Ethics Review Committees of Youjiang Medical University for Nationalities and carried out in accordance with the approved guidelines (No. AYJM20210708).
Informed consent statement: Informed consent from the patients was waived due to the retrospective nature of this study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Xi-Dai Long, MD, PhD, Professor, Research Scientist, Clinicopathological Diagnosis and Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. sjtulongxd@ymun.edu.cn
Received: March 6, 2024
Revised: June 27, 2024
Accepted: July 10, 2024
Published online: August 27, 2024
Processing time: 168 Days and 21.4 Hours
Abstract
BACKGROUND

The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC).

AIM

To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC.

METHODS

A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis.

RESULTS

Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.

CONCLUSION

These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

Keywords: Tissue inhibitor of metalloproteinase-3 expression; Aflatoxin B1; Hepatocellular carcinoma; Clinicopathological feature; Prognosis

Core Tip: This study retrospectively analyzed tissue inhibitor of metalloproteinase-3 (TIMP3) expression and the clinicopathological characteristics and prognosis of aflatoxin B1-related hepatocellular carcinoma (AHCC). It was found that TIMP3 expression was statistically associated with the prognosis of AHCC as an independent risk factor. The dysregulation of TIMP3 expression affected the clinicopathological features and has great value to predict the prognosis of AHCC.