Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2023; 11(15): 3444-3456
Published online May 26, 2023. doi: 10.12998/wjcc.v11.i15.3444
Establishment of a prognostic model related to tregs and natural killer cells infiltration in bladder cancer
Yan-Jie Yang, Xiao-Qing Xu, Yi-Chao Zhang, Peng-Cheng Hu, Wu-Xia Yang
Yan-Jie Yang, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, China
Xiao-Qing Xu, The Graduate School, Tianjin Medical University, Tianjin 300041, China
Yi-Chao Zhang, The Graduate School, Qinghai University, Xi'ning 810000, Qinghai Province, China
Peng-Cheng Hu, Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Wu-Xia Yang, The Graduate School/Department of Traditional Chinese Medicine, Tianjin Medical University/Tianjin Medical University General Hospital, Tianjin 300041, China
Author contributions: Yang YJ and Xu XQ designed and coordinated the study; Yang YJ performed the experiments, acquired, and analyzed data; Xu XQ, Zhang YC, and Hu PC interpreted the data; Yang YJ, Xu XQ, and Yang WX wrote the manuscript; all authors approved the final version of the article; Yang YJ and Xu XQ contributed equally to this work.
Institutional review board statement: Nor ethical approval nor informed consent was required in this study due to the public available of date in the WGCNA, GEO, and TCIA databases (https://portal.gdc.cancer.gov/ and https://www.ncbi.nlm.nih.gov/geo/).
Conflict-of-interest statement: There is no conflict of interest between the authors.
Data sharing statement: All authors agree to data sharing.
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: Wu-Xia Yang, MM, Doctor, The Graduate School/Department of Traditional Chinese Medicine, Tianjin Medical University/Tianjin Medical University General Hospital, Tianjin 300041, China. yangwuxia_09@tmu.edu.cn
Received: December 16, 2022
Peer-review started: December 16, 2022
First decision: February 28, 2023
Revised: March 8, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 26, 2023
Processing time: 160 Days and 4.2 Hours
Abstract
BACKGROUND

Regulatory T cells (Tregs) and natural killer (NK) cells play an essential role in the development of bladder urothelial carcinoma (BUC).

AIM

To construct a prognosis-related model to judge the prognosis of patients with bladder cancer, meanwhile, predict the sensitivity of patients to chemotherapy and immunotherapy.

METHODS

Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894. The CIBERSORT was used to calculate the immune score of each sample. Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns. Subsequently, multivariate cox regression and lasso regression was used to further screen prognosis-related genes. The prrophetic package was used to predict phenotype from gene expression data, drug sensitivity of external cell line and predict clinical data.

RESULTS

The stage and risk scores are independent prognostic factors in patients with BUC. Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor, and additionally, EMP1, TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints, while CMTM8, SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.

CONCLUSION

Prognosis-related models of bladder tumor patients, based on Treg and NK cell percolation in tumor tissue. In addition to judging the prognosis of patients with bladder cancer, it can also predict the sensitivity of patients to chemotherapy and immunotherapy. At the same time, patients were divided into high and low risk groups based on this model, and differences in genetic mutations were found between the high and low risk groups.

Keywords: Natural killer cells, Tregs, Bladder cancer, Weighted gene coexpression network analysis, Bladder cancer treatment, Immunotherapy, Computational molecular biology

Core Tip: Tregs are thought to be connected to tumor cells evading the immune system, which is linked to cancer patients' poor prognoses. Natural killer (NK) cells control different immune responses and show antitumor cytotoxicity without being previously sensitized. We determined the immunological scores of several cell types in bladder urothelial carcinoma, discovered a gene set that was favorably connected with the Tregs score and negatively correlated with the NK cells score, and built a model that was related to prognosis. The model can predict the sensitivity of patients to chemotherapy and immunotherapy in addition to their prognosis for bladder cancers.