Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1675-1688
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1675
Potential of six-transmembrane epithelial antigen of the prostate 4 as a prognostic marker for colorectal cancer
Ze-Xuan Fang, Chun-Lan Li, Wen-Jia Chen, Hua-Tao Wu, Jing Liu
Ze-Xuan Fang, Chun-Lan Li, Wen-Jia Chen, Jing Liu, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Hua-Tao Wu, Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Author contributions: Liu J and Wu HT designed the research study; Fang ZX performed the research; Fang ZX, Li CL, Chen WJ, and Wu HT analyzed the research and wrote the manuscript; Liu J revised the manuscript critically; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81501539; the Natural Science Foundation of Guangdong Province, No. 2021A1515012180 and 2016A030312008; the Special Grant for Key Area Programs of Guangdong Department of Education, No. 2021ZDZX2004; the Science and Technology Special Project of Guangdong Province, No. 210715216902829; and “Dengfeng Project” for the Construction of High-level Hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding, No. 202003-10.
Institutional review board statement: The current study was reviewed and approved by the Ethics Committee of Shantou University Medical College.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are 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: Jing Liu, MD, PhD, Academic Research, Associate Professor, Research Scientist, Senior Scientist, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong Province, China. jliu12@stu.edu.cn
Received: January 18, 2022
Peer-review started: January 18, 2022
First decision: March 8, 2022
Revised: March 23, 2022
Accepted: August 6, 2022
Article in press: August 6, 2022
Published online: September 15, 2022
Abstract
BACKGROUND

Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers (CRC). Human six-transmembrane epithelial antigen of the prostate (STEAP) proteins have been recognized and utilized as promising targets for cell- and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.

AIM

To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.

METHODS

The expression level of STEAPs in CRC was evaluated using various open-resource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immune-related biomarkers, such as immune infiltration. Immunohistochemical (IHC) experiments were subsequently performed to verify the database conclusions.

RESULTS

The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However, STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.

CONCLUSION

Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.

Keywords: Six-transmembrane epithelial antigen of the prostate, Colorectal cancer, Immunotherapy, Target, Survival

Core Tip: This study analyzed the expression levels of six-transmembrane epithelial antigen of the prostate (STEAP) family members in colorectal cancer (CRC) and explored the potential biological function of STEAP4. It was found that the expression of STEAP4 in CRC tissues had a positive correlation with immune infiltration and immune-related biomarkers, such as MLH1, MLH6, and PMS2, and a negative correlation with programmed death ligand 1. STEAP4 is expected to be a novel and potential prognostic biomarker for CRC.