Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2022; 10(21): 7242-7255
Published online Jul 26, 2022. doi: 10.12998/wjcc.v10.i21.7242
Expression of hepatocyte nuclear factor 4 alpha, wingless-related integration site, and β-catenin in clinical gastric cancer
Qian Hu, Ling-Li Li, Ze Peng, Ping Yi
Qian Hu, Ling-Li Li, Ze Peng, Ping Yi, Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Yi P designed the study; Hu Q, Li LL and Peng Z conducted the experiments; Hu Q wrote and revised the manuscript; Yi P checked the pathological results; and All authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 81673757.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional date is available.
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: Ping Yi, MD, PhD, Doctor, Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China. pyi219@163.com
Received: March 25, 2022
Peer-review started: March 25, 2022
First decision: April 13, 2022
Revised: April 17, 2022
Accepted: June 3, 2022
Article in press: June 3, 2022
Published online: July 26, 2022
Processing time: 108 Days and 5.7 Hours
Abstract
BACKGROUND

Gastric cancer (GC) is the second most common cause of cancer-related deaths worldwide. Hepatocyte nuclear factor 4 alpha (HNF4α) that belongs to the nuclear hormone receptor superfamily, is overexpressed in GC tissues, and might be involved in the development of GC by regulating its downstream wingless-related integration site (WNT)/β-catenin signaling.

AIM

To clarify the expression of HNF4α/WNT5a/β-catenin signaling proteins in clinical GC tissues.

METHODS

We immunohistochemically stained pathological blocks of GC and matched para-cancerous tissues. The intensity of HNF4α, WNT5a and β-catenin staining in the tumor cells was determined according to cell rates and staining intensity. The correlations between GC and HNF4α, WNT5a, and β-catenin expression using chi-square and paired chi-square tests. Relationships between double-positive HNF4α and WNT5a expression and types of gastric tumor tissues were assessed using regression analysis. Correlations between HNF4α and WNT5a expression at the RNA level in GC tissues found in the TCGA database were analyzed using Pearson correlation coefficients.

RESULTS

We found more abundant HNF4α and WNT5a proteins in GC, especially in mucinous adenocarcinoma and mixed GC than in adjacent tissues (P < 0.001). Low and high levels of cytoplasmic β-catenin respectively expressed in GC and adjacent tissues (P < 0.001) were not significantly associated with pathological parameters.

CONCLUSION

The expressions of HNF4α and WNT5a could serve as early diagnostic biomarkers for GC.

Keywords: β-catenin; Biomarker; Gastric cancer; Hepatocyte nuclear factor 4 alpha; Wingless-related integration site

Core Tip: Gastric cancer (GC) is the second most common cause of cancer-related deaths worldwide. A precise biopsy biomarker that can predict the progression of GC and change its prognosis is urgently needed. We previously found that hepatocyte nuclear factor 4 alpha (HNF4α)/wingless-related integration site (WNT) signaling is involved in the process of GC in preclinical models. Here, we obtained gastric tumor and para-cancerous tissue sections from Tongji Hospital and investigated the expression of HNF4α, WNT5a, and β-catenin. The expression of HNF4α and WNT5a could serve as an early diagnostic biomarker of GC.