The role of TGR5 as an onco-immunological biomarker in tumor staging and prognosis by encompassing the tumor microenvironment

Our plain-English summary of The role of TGR5 as an onco-immunological biomarker in tumor staging and prognosis by encompassing the tumor microenvironment, by Z. Guan, L. Luo, S. Liu, et al (Frontiers in Oncology, 2022).

The study

• Authors: Z. Guan, L. Luo, S. Liu, Z. Guan, Q. Zhang, Z. Wu, K. Tao
• Journal: Frontiers in Oncology
• Published: 2022;12:953091
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The relationship between G protein-coupled bile acid receptor 1 (TGR5, GPBAR1) and, specifically, cancer has been studied in in vivo and in vitro 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.

Copyright © 2022 Guan, Luo, Liu, Guan, Zhang, Wu and Tao.

In plain English

This article was a database study of a gene called TGR5 (also called GPBAR1), a bile acid receptor, across 33 tumor types in The Cancer Genome Atlas and other public databases. It did not study asbestos or any fiber exposure. The authors compared the level of TGR5 gene expression in tumor and normal tissue. They found expression higher in several cancers, such as bladder and breast cancers, and lower in cholangiocarcinoma and glioblastoma. Patients were then split into high-TGR5 and low-TGR5 groups. High TGR5 was linked to poorer overall survival in five cancers, including glioblastoma (p = 0.0048). Low TGR5 was linked to poorer overall survival in four cancers, including malignant mesothelioma (MESO), with p = 0.048. The article did not say whether these mesotheliomas were pleural or peritoneal, and it gave no patient numbers. In cultured cells, TGR5 increased the activity of renal cell carcinoma cells and reduced the activity of skin cancer and osteosarcoma cells. The authors concluded that their analysis strengthened the idea of a statistical correlation between TGR5 and prognosis, and they called the findings preliminary.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pan-cancer bioinformatics analysis of public gene-expression databases (TCGA, GEO, GEPIA2, TIMER2, cBioPortal, Human Protein Atlas), plus cell-line experiments
• Who was studied: Tumor and normal tissue data for 33 cancer types in The Cancer Genome Atlas and related databases; the number of patients is not given. Cell experiments used skin basal cell carcinoma, osteosarcoma (MG-63) and renal cancer (Caki-1, 786-O) cell lines, with n = 8 per group.
• Exposure: Level of TGR5 (GPBAR1) gene expression, split into high and low groups at the median. No asbestos or fiber exposure was studied.
• Main results:
  • TGR5 gene expression was lower than in the corresponding normal tissue in cholangiocarcinoma and glioblastoma multiforme (p < 0.001). It was higher in several other cancers, including bladder and breast cancers.
  • High TGR5 expression was related to poorer overall survival in glioblastoma (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).
  • Lower TGR5 expression was linked with poorer overall survival in cervical cancer (p = 0.014), malignant mesothelioma (MESO, p = 0.048), sarcoma (p = 0.018) and skin cutaneous melanoma (p = 0.0085).
  • In disease-free survival analysis, high TGR5 expression was associated with poorer prognosis in glioblastoma (p = 0.0029) and uveal melanoma (p = 0.046).
  • In uveal melanoma, TGR5 expression was negatively correlated with the infiltration level of M2 macrophages as estimated by the TIDE method (correlation −0.541).
  • In cell experiments, TGR5 increased the activity of renal cell carcinoma cells and reduced the activity of skin cancer and osteosarcoma cells.
• The authors' conclusion: The authors concluded that the pan-cancer analysis strengthened the idea of a statistical correlation of TGR5 with gene expression, clinical prognosis, genetic alteration, tumor mutation burden, immune cell infiltration and microsatellite instability.
• Limitations the authors state:
  • Methylation levels and prognosis were analyzed for only four cancers.
  • The authors described the findings as preliminary and needing further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Staging, Prognosis, Tumor Microenvironment, Overall Survival, Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma.

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