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Original Article

Korean J Physiol Pharmacol 2023; 27(3): 241-256

Published online May 1, 2023 https://doi.org/10.4196/kjpp.2023.27.3.241

Copyright © Korean J Physiol Pharmacol.

MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors

Wen An1, Ju-Seop Kang1,*, Sukjoong Oh2, and Ang Tu3

1Department of Pharmacology & Clinical Pharmacology Lab, 2Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Korea, 3Department of Pharmacy, Xiantao Hospital of Traditional Chinese Medicine, Xiantao 433000, China

Correspondence to:Ju-Seop Kang
E-mail: jskang@hanyang.ac.kr

Author contributions: W.A. designed the model and the computational framework, analyzed the data, and wrote the original draft. J.S.K. was involved in planning, supervision, and editing of manuscript drafts. S.O. was involved in supervision of data analyses. A.T. participated in data collection.

Received: January 5, 2023; Revised: March 15, 2023; Accepted: March 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CAR-T cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF-β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF-β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

Keywords: Adenocarcinoma of lung, Breast neoplasms, Chimeric antigen receptor T cell, RON protein, Urinary bladder neoplasms