Guan Zhiyuan, Luo Liying, Liu Shengfu, Guan Zhiqiang, Zhang Qinggang, Wu Zhong, Tao Kun
Department of Orthopedics, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
Department of Ophthalmology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2022 Oct 20;12:953091. doi: 10.3389/fonc.2022.953091. eCollection 2022.
The relationship between G protein-coupled bile acid receptor 1 (TGR5, GPBAR1) and, specifically, cancer has been studied in and experiments, but there is still a lack of pan-cancer analysis to understand the prognostic significance and functioning mechanism of TGR5 in different cancer-driving oncogenic processes. Here, we used Gene Expression Integration, Human Protein Atlas, and The Cancer Genome Atlas (TCGA) to perform a pan-cancer analysis of the role of TGR5 in all 33 tumors. In all TCGA tumors, the TGR5 gene expression has been assessed, and we found that the high TGR5 gene expression in most cancers is associated with poor prognosis of overall survival for cancers such as glioblastoma multiforme (p = 0.0048), kidney renal papillary cell carcinoma (p = 0.033), lower grade glioma (p = 0.0028), thymoma (p = 0.048), and uveal melanoma (p = 0.004), and then the lower expression of TGR5 was linked with poor prognosis in cervical squamous cell carcinoma and endocervical adenocarcinoma (p = 0.014), malignant mesothelioma (MESO) (p = 0.048), sarcoma (p = 0.018), and skin cutaneous melanoma (p = 0.0085). The TGR5 expression was linked with the immune infiltration level of the macrophage M2_TIDE and was also associated with DNA methylation in ovarian and breast cancers. The regulation of hormone secretion, Rap1 pathway, osteoclast differentiation, and bile acid pathway was involved in the functional mechanism of TGR5. Besides, gene expressions were different in different tumors detected by RT-PCR, and cell activity experiments have also found that TGR5 can increase the activity of renal cell carcinoma and reduce the activity of skin cancer and osteosarcoma cells. In this investigation, the aim was to assess the comprehensive overview of the oncogenic roles of TGR5 in all TCGA tumors using pan-analysis.
在[具体实验1]和[具体实验2]中研究了G蛋白偶联胆汁酸受体1（TGR5，GPBAR1）与癌症之间的关系，但仍缺乏泛癌分析来了解TGR5在不同癌症驱动致癌过程中的预后意义和作用机制。在此，我们使用基因表达整合、人类蛋白质图谱和癌症基因组图谱（TCGA）对TGR5在所有33种肿瘤中的作用进行泛癌分析。在所有TCGA肿瘤中，均对TGR5基因表达进行了评估，我们发现，在大多数癌症中，TGR5基因高表达与多形性胶质母细胞瘤（p = 0.0048）、肾肾乳头状细胞癌（p = 0.033）、低级别胶质瘤（p = 0.0028）、胸腺瘤（p = 0.048）和葡萄膜黑色素瘤（p = 0.004）等癌症的总生存期预后不良相关，而在宫颈鳞状细胞癌和宫颈管腺癌（p = 0.014）、恶性间皮瘤（MESO）（p = 0.048）、肉瘤（p = 0.018）和皮肤黑色素瘤（p = 0.0085）中，TGR5低表达与预后不良相关。TGR5表达与巨噬细胞M2_TIDE的免疫浸润水平相关，并且在卵巢癌和乳腺癌中也与DNA甲基化有关。激素分泌调节、Rap1通路、破骨细胞分化和胆汁酸通路参与了TGR5的功能机制。此外，通过RT-PCR检测发现不同肿瘤中的基因表达存在差异，细胞活性实验还发现TGR5可增加肾癌细胞的活性，并降低皮肤癌和骨肉瘤细胞的活性。在本研究中，目的是通过泛分析评估TGR5在所有TCGA肿瘤中的致癌作用的全面概况。
