Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 24, 2025; 16(4): 102958
Published online Apr 24, 2025. doi: 10.5306/wjco.v16.i4.102958
Downregulation of huntingtin-associated protein 1 predicts poor prognosis in gastric cancer
Xiang-Yang Wang, Fu-Hai Yang, Zhong-Yuan Yuan, Zhong-Jing Wang, Hong-Feng Zhang, Zi-Hui Xu
Xiang-Yang Wang, Fu-Hai Yang, Zhong-Yuan Yuan, Department of Gastrointestinal Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Zhong-Jing Wang, Zi-Hui Xu, Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Hong-Feng Zhang, Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Co-corresponding authors: Hong-Feng Zhang and Zi-Hui Xu.
Author contributions: Wang XY, Yang FH, and Yuan ZY conducted the experiments; Zhang HF and Xu ZH designed experiments; Wang XY, Zhang HF, and Xu ZH analyzed the data; Wang XY, Yang FH, Yuan ZY, Wang ZJ, Zhang HF, Xu ZH drafted and approved the manuscript; Zhang HF and Xu ZH are co-corresponding authors of this manuscript, contributing equally to manuscript revision.
Supported by the Hubei Province Natural Science Foundation Project, No. 2021CFB448; and the Wuhan Municipal Health Commission, No. WX23A55.
Institutional review board statement: All procedures involving human participants in this study were in accordance with the ethical standards of the institutional and national research committee. The Ethics Committee of Central Hospital of Wuhan approved this study (No. WHZXKYL2024-207).
Institutional animal care and use committee statement: This study is not involving animal subjects.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: All the data are available without resection. Researchers can obtain data by contacting the corresponding author.
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: Zi-Hui Xu, MD, PhD, Associate Chief Physician, Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Wuhan 430014, Hubei Province, China. tj017@163.com
Received: November 7, 2024
Revised: January 18, 2025
Accepted: February 24, 2025
Published online: April 24, 2025
Processing time: 143 Days and 15.3 Hours
Abstract
BACKGROUND

Highly expressed in the gastrointestinal mucosa, huntingtin-associated protein 1 (HAP1) is closely associated with tumor development and prognosis.

AIM

To investigate the clinical utility of HAP1 expression in gastric cancer (GC).

METHODS

We randomly selected 124 GC patients had not undergone preoperative radiotherapy or chemotherapy, they were diagnosed at the Central Hospital of Wuhan between May 2013 and October 2018. Immunohistochemistry was used to detect HAP1 expression in paraffin-embedded GC tissues, as well as metastatic lymph nodes. Their clinical data were collected and all participants were follow up for 5 years. Western blotting and quantitative polymerase chain reaction were used to detect HAP1 levels in 20 matched pairs of fresh GC tissues.

RESULTS

HAP1 protein and mRNA levels were lower in fresh GC tissues than in normal mucosal tissues (P < 0.001, respectively). Immunohistochemistry also revealed lower HAP1 expression in GC tissues and metastatic lymph nodes than in normal mucosal tissues (P < 0.05). HAP1 expression in GC was closely associated with differentiation, lymph node metastasis, lymph node ratio, remote metastasis, clinical stage, tumor location, and survival time (P < 0.05). Furthermore, HAP1 expression independently predicted GC (P < 0.05) and was more accurate in advanced GC than in early GC (P < 0.05).

CONCLUSION

HAP1 is an important prognostic biomarker for GC, with low HAP1 expression positively correlating with poor overall survival, especially in advanced clinical stages.

Keywords: Huntingtin-associated protein 1; Gastric cancer; Prognostic utility; Biomarker; Clinical stage

Core Tip: The clinical utility of huntingtin-associated protein 1 (HAP1) expression in gastric cancer (GC) was assessed. HAP1 expression was significantly lower in GC tissues than in normal gastric mucosa, and was strongly associated with GC progression and metastasis. Downregulation of HAP1 correlates with poor overall survival in patients with GC, especially in advanced clinical stages. Thus, HAP1 is a promising prognostic marker for GC, with important implications for advancing treatment.