Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1578-1595
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1578
Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer: A systematic review and meta-analysis
Eric Toshiyuki Nakamura, Amanda Park, Marina Alessandra Pereira, Daniel Kikawa, Francisco Tustumi
Eric Toshiyuki Nakamura, Marina Alessandra Pereira, Francisco Tustumi, Department of Gastroenterology, Instituto do Câncer, Hospital das Clínicas da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246000, Brazil
Eric Toshiyuki Nakamura, Daniel Kikawa, Department of Scientific Initiation, Universidade Mogi das Cruzes, São Paulo 08780911, Brazil
Amanda Park, Department of Evidence-Based Medicine, Centro Universitário Lusíada, Centre for Evidence-Based Medicine, Centro Universitário Lusíada (UNILUS), Santos, Brazil
Francisco Tustumi, Department of Surgery, Hospital Israelita Albert Einstein, São Paulo 05652900, Brazil
Author contributions: Tustumi F designed the research, analyzed the data; Nakamura ET, Park A, and Tustumi F wrote the paper; Nakamura ET and Park A performed the research; Pereira MA and Kikawa D assisted in the research and reviewed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Francisco Tustumi, MD, PhD, Surgeon, Surgical Oncologist, Department of Surgery, Hospital Israelita Albert Einstein, Avenue Albert Einstein, 627/701 - Morumbi, São Paulo 05652900, Brazil. franciscotustumi@gmail.com
Received: October 8, 2023
Peer-review started: October 8, 2023
First decision: December 15, 2023
Revised: December 24, 2023
Accepted: January 23, 2024
Article in press: January 23, 2024
Published online: April 15, 2024
Processing time: 186 Days and 1 Hours
Abstract
BACKGROUND

Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed in many cancers. The prognostic significance of HSPs and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, are poorly understood.

AIM

To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.

METHODS

A systematic review was conducted in accordance with PRISMA recommendations (PROSPERO: CRD42022370653), on Embase, PubMed, Cochrane, and LILACS. Cohort, case-control, and cross-sectional studies of patients with esophagus or esophagogastric cancer were included. HSP-positive patients were compared with HSP-negative, and the endpoints analyzed were lymph node metastasis, tumor depth, distant metastasis, and overall survival (OS). HSPs were stratified according to the HSP family, and the summary risk difference (RD) was calculated using a random-effect model.

RESULTS

The final selection comprised 27 studies, including esophageal squamous cell carcinoma (21), esophagogastric adenocarcinoma (5), and mixed neoplasms (1). The pooled sample size was 3465 patients. HSP40 and 60 were associated with a higher 3-year OS [HSP40: RD = 0.22; 95% confidence interval (CI): 0.09-0.35; HSP60: RD = 0.33; 95%CI: 0.17-0.50], while HSF1 was associated with a poor 3-year OS (RD = -0.22; 95%CI: -0.32 to -0.12). The other HSP families were not associated with long-term survival. HSF1 was associated with a higher probability of lymph node metastasis (RD = -0.16; 95%CI: -0.29 to -0.04). HSP40 was associated with a lower probability of lymph node dissemination (RD = 0.18; 95%CI: 0.03-0.33). The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.

CONCLUSION

The expression levels of certain families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Keywords: Heat-shock proteins; Heat-shock response; Prognosis; Esophageal neoplasms; Meta-analysis

Core Tip: Heat shock proteins (HSPs) and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, play an important role in cellular protection against stress events, and are overexpressed in some types or cancer. However, the prognostic significance of HSPs remains unclear. In the present study, we conducted a systematic review and meta-analysis to investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer that included 27 studies. Our findings demonstrated that the expression levels of some families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in esophageal cancer.