An Wen, Kang Ju-Seop, Oh Sukjoong, Tu Ang
Department of Pharmacology & Clinical Pharmacology Lab, Hanyang University, Seoul 04763, Korea.
Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Korea.
Korean J Physiol Pharmacol. 2023 May 1;27(3):241-256. doi: 10.4196/kjpp.2023.27.3.241.
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.
尽管嵌合抗原受体T细胞（CAR-T）在血液系统恶性肿瘤中是一种很有前景的免疫疗法，但CAR-T细胞疗法用于实体瘤仍存在许多障碍。识别合适的肿瘤相关抗原（TAA）对成功尤为关键。我们采用生物信息学方法，确定了实体瘤中CAR-T细胞免疫疗法的常见潜在TAA。我们将GEO数据库用作训练数据集来寻找差异表达基因（DEG），并使用TCGA数据库验证候选基因，获得了7个常见的DEG（HM13、SDC1、MST1R、HMMR、MIF、CD24和PDIA4）。然后，我们使用MERAV分析6个基因在正常组织中的表达，以确定理想的靶基因。最后，我们分析了肿瘤微环境因素。主要微环境因素分析结果显示，MDSC、CXCL1、CXCL12、CXCL5、CCL2、CCL5、TGF-β、CTLA-4和IFN-γ在乳腺癌中显著过表达。MST1R的表达与TGF-β、CTLA-4和IFN-γ呈正相关。在肺腺癌中，MDSC、Treg、CXCL12、CXCL5、CCL2、PD-L1、CTLA-4和IFN-γ在肿瘤组织中显著过表达。MST1R的表达与TGF-β、CTLA-4和IFN-γ呈正相关。在膀胱癌中，CXCL12、CCL2和CXCL5在肿瘤组织中显著过表达。MST1R表达与TGF-β呈正相关。我们的结果表明，MST1R有潜力作为治疗乳腺癌、肺腺癌和膀胱癌的新靶抗原，并且可能用作膀胱癌的进展指标。
