Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Sep 20, 2023; 13(4): 223-237
Published online Sep 20, 2023. doi: 10.5662/wjm.v13.i4.223
Comprehensive analysis of cell-extracellular matrix protein Ras suppressor-1 in function and prognosis of gastrointestinal cancers
Ya Xu, Yan-Yu Hou, Zheng Wu, Ze-Xuan Fang, Hua-Tao Wu, Jing Liu
Ya Xu, Department of Radiation Oncology, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei 516600, Guangdong Province, China
Yan-Yu Hou, Zheng Wu, Ze-Xuan Fang, 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: Xu Y and Liu J contributed to the study conception and design. Material preparation, data collection and analysis were performed by Xu Y, Hou YY, Wu Z, Fang ZX, and Wu HT; The first draft of the manuscript was written by Xu Y and all authors commented on previous versions of the manuscript; As the corresponding author, Liu J is the general person in charge of the project, responsible for the project funding, design, writing and checking of the article; All authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82273457; the Natural Science Foundation of Guangdong Province, No. 2023A1515012762; and 2021A1515012180; Special Grant for Key Area Programs of Guangdong Department of Education, No. 2021ZDZX2040; Science and Technology Special Project of Guangdong Province, No. 210715216902829.
Institutional review board statement: In current manuscript, NO-animal experiment was conducted, or NO-Human Participants was involved. So, we did not apply the approval form or document from the committee. Meanwhile, the ARRIVE guidelines were not appropriate for this article.
Conflict-of-interest statement: No conflict of interest is claimed by any author.
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: March 27, 2023
Peer-review started: March 27, 2023
First decision: May 25, 2023
Revised: June 6, 2023
Accepted: June 19, 2023
Article in press: June 19, 2023
Published online: September 20, 2023
Processing time: 176 Days and 21.7 Hours
Abstract
BACKGROUND

Ras suppressor 1 (RSU1), a highly conserved protein, plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion. Aberration of RSU1 activity can cause changes in cell adhesion and migration, thereby enhancing tumor proliferation and metastasis. However, the correlation between RSU1 and gastrointestinal cancers (GICs), as well as its prognostic role related to tumor-infiltrating immune cells (TIICs) remains unclear.

AIM

To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.

METHODS

Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter. Then, RSU1-correlated genes were screened and functionally characterized via enrichment analysis. The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource (TIMER). In addition, the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.

RESULTS

High RSU1 expression was associated with poor overall survival of gastric cancer patients, exhibiting a hazard ratio (HR) = 1.36, first progression HR = 1.53, and post progression survival HR = 1.6. Specifically, high RSU1 Levels were associated with prognosis of gastric cancer in females, T4 and N3 stages, and Her-2-negative subtypes. Regarding immune-infiltrating cells, RSU1 expression level was positively correlated with infiltration of CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colorectal adenocarcinoma and stomach adenocarcinoma. RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage, DCs and T cell exhaustion in GICs.

CONCLUSION

In gastrointestinal cancers, RSU1 is increased in tumor tissues, and predicts poor survival of patients. Increased RSU1 may be involved in promoting macrophage polarization, DC infiltration, and T cell exhaustion, inducing tumor immune escape and the development of tumors in GICs. We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs, as well as a potential therapeutic target for precision treatment through improving the immune response.

Keywords: Ras suppressor 1; Gastrointestinal cancer; Immune infiltration; Prognosis; Actin cytoskeleton remodeling

Core Tip: Ras suppressor 1 (RSU1), is a highly conserved protein involved in actin cytoskeleton remodeling and cell-extracellular matrix adhesion. The current study provides a comprehensive analysis of RSU1 in gastrointestinal cancer and shows its potential promoting role in facilitating tumor immune escape.