Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2023; 14(8): 297-310
Published online Aug 24, 2023. doi: 10.5306/wjco.v14.i8.297
Immune responses of six-transmembrane epithelial antigen of the prostate 4 functions as a novel biomarker in gastric cancer
Ze-Xuan Fang, Yan-Yu Hou, Zheng Wu, Bing-Xuan Wu, Yu Deng, Hua-Tao Wu, Jing Liu
Ze-Xuan Fang, Yan-Yu Hou, Zheng Wu, 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
Bing-Xuan Wu, Yu Deng, Hua-Tao Wu, Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Author contributions: Liu J and Fang ZX designed the research study; Fang ZX performed the research; Fang ZX, Hou YY, Wu Z, Wu BX, Deng Y, 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. 82273457 and No. 81501539; Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515012762 and No. 2021A1515012180; Special Grant for Key Area Programs of Guangdong Department of Education, No. 2021ZDZX2040; and Science and Technology Special Project of Guangdong Province, No. 210715216902829.
Institutional review board statement: The current study was reviewed and approved by the Ethics Committee of Shantou University Medical College (Approval No. SUMC-2022-075).
Informed consent statement: The informed consent was waived by the Ethics Committee because our experiment was conducted on commercial microarray.
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, China. jliu12@stu.edu.cn
Received: May 10, 2023
Peer-review started: May 10, 2023
First decision: June 7, 2023
Revised: June 19, 2023
Accepted: July 19, 2023
Article in press: July 19, 2023
Published online: August 24, 2023
ARTICLE HIGHLIGHTS
Research background

Six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a transmembrane protein involved in metal reductase transport of copper and iron, has been reported as a potential target for cellular and antibody immunotherapy.

Research motivation

Few studies on STEAP4 in gastric cancer (GC), which may play a role in the immune response to the occurrence and development of GC.

Research objectives

The expression of STEAP4 in GC tissues and its correlation with the level of tumor immune infiltration were comprehensively analyzed and to explore the potential immune effect of STEAP4 in GC.

Research methods

The protein expression level, clinicopathological parameters and prognosis of STEAP4 in tumor and adjacent tissues of GC patients were detected by immunohistochemistry. An online database was used to study the correlation between STEAP4 and the level of tumor immunoinfiltration and the characteristics of immunoinfiltration genes. The relationship between STEAP4 expression and immune and stromal scores in the GC was analyzed by ESTIMATE algorithm.

Research results

Immunohistochemistry analysis showed that STEAP4 was highly expressed in GC and was positively correlated with the clinical stage of GC. The infiltration levels of immune cells such as B cells, CD4+ T cells, macrophages, neutrophils and dendritic cells were positively correlated with STEAP4. The expression level of STEAP4 was strongly correlated with most of the immune markers. In addition, the ESTIMATED algorithm analysis showed that the stromal, immune and estimated scores were higher in the group with high expression of STEAP4, while the tumor purity was higher in the STEAP4 Low expression group. The relationship between STEAP4 expression and prognosis of GC patients was further studied, and the results showed that high STEAP4 expression had shorter overall survival and disease-free survival. Moreover, Kaplan-Meier Plotter showed that high expression of STEAP4 was associated with poor survival in patients with GC.

Research conclusions

STEAP4 is indicated as a potential immune indicator of GC, targeting STEAP4 may provide a new therapeutic method for GC patients.

Research perspectives

The comprehensive analysis of STEAP4 function in GC still needs to explore the mechanism by which STEAP4 plays an immune role in GC.