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MST1R 作为 CAR-T 细胞治疗实体瘤的潜在新靶抗原

英文原题:MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors.

PubMed 2023/05/01(内容时间) Korean J Physiol Pharmacol Q3 · IF 2.5(JCR 2025)

研究概要

我们的结果证明,MST1R 有潜力作为治疗乳腺癌、肺腺癌和膀胱癌的新靶抗原,并可能用作膀胱癌的进展指标。

中文摘要

CAR-T是治疗血液恶性肿瘤的有前景免疫疗法,但其用于实体瘤仍有许多障碍,尤其需找到合适肿瘤相关抗原(TAA)。研究者采用生物信息学方法寻找实体瘤CAR-T共同潜在TAA。以GEO为训练数据筛选差异表达基因,再用TCGA验证,得到7个共同差异基因:HM13、SDC1、MST1R、HMMR、MIF、CD24和PDIA4。随后用MERAV分析其中6个基因在正常组织中的表达,以确定理想靶点,并分析肿瘤微环境。乳腺癌中MDSC、CXCL1、CXCL12、CXCL5、CCL2、CCL5、TGF-β、CTLA-4和IFN-γ显著过表达;MST1R与TGF-β、CTLA-4和IFN-γ正相关。肺腺癌中MDSC、Treg、CXCL12、CXCL5、CCL2、PD-L1、CTLA-4和IFN-γ升高,MST1R同样与TGF-β、CTLA-4和IFN-γ正相关。膀胱癌中CXCL12、CCL2和CXCL5显著过表达,MST1R与TGF-β正相关。结果提示MST1R可能成为治疗乳腺癌、肺腺癌和膀胱癌的新靶抗原,也可能作为膀胱癌进展指标。

展开英文摘要原文

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- , CTLA-4, and IFN- were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- , CTLA-4, and IFN- . In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN- were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- , CTLA-4, and IFN- . In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- . 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.

论文信息

作者
An W、Kang JS、Oh S、Tu A
第一作者单位
Department of Pharmacology & Clinical Pharmacology Lab, Hanyang University, Seoul 04763, Korea.South Korea
通讯作者单位
Department of Pharmacy, Xiantao Hospital of Traditional Chinese Medicine, Xiantao 433000, China.China
期刊
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2023 May 1
原文标识
PubMed 37078298 · DOI 10.4196/kjpp.2023.27.3.241