Prognostic Implications of Pan-Cancer CMTM6 Expression and Its Relationship with the Immune Microenvironment

Our plain-English summary of Prognostic Implications of Pan-Cancer CMTM6 Expression and Its Relationship with the Immune Microenvironment, by Y. Zhao, M. Zhang, H. Pu, et al (Frontiers in Oncology, 2020).

The study

• Authors: Y. Zhao, M. Zhang, H. Pu, S. Guo, S. Zhang, Y. Wang
• Journal: Frontiers in Oncology
• Published: 2020;10:585961
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) reportedly stabilizes programmed death-ligand 1 (PD-L1) and enhances the efficacy of immunotherapy. However, correlations between CMTM6 expression and the immune microenvironment and its prognostic value remain unknown in a variety of tumors. CMTM6 expression data were obtained from The Cancer Genome Atlas (TCGA) for 33 cancer types classified into high and low expression subgroups according to the median CMTM6 expression value. Pan-cancer analysis of CMTM6 protein expression in 20 tumor types was performed using a cohort from the Human Protein Atlas (HPA). PD-L1 protein expression data were obtained from The Cancer Proteome Atlas (TCPA) for 32 cancer types. Frequencies of CMTM6 copy number alterations and mutations were analyzed using cBioPortal. MANTIS was employed to estimate microsatellite instability in the TCGA cohort. CIBERSORT and the ESTIMATE algorithm were applied to estimate the relative fractions of infiltrating immune cell types and immune scores, respectively. Kaplan-Meier survival curve analysis was performed to assess the pan-cancer prognostic value of CMTM6.CMTM6 is heterogeneously expressed in diverse cancers. Further, the results revealed low CMTM6 mutation frequencies in multiple cancers. Among them, CMTM6 mutation frequency was the highest in uterine cancer. Additionally, CMTM6 expression was related to PD-L1 protein expression in breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, sarcoma (SARC), stomach adenocarcinoma, and uterine carcinosarcoma. Increased CMTM6 expression may be associated with increased infiltration of neutrophils in some types of cancer. Finally, pan-cancer analysis indicated that CMTM6 expression was closely related to overall survival in adrenocortical carcinoma, GBM, acute myeloid leukemia, liver hepatocellular carcinoma, mesothelioma, SARC, thymoma, and uveal melanoma. Taken together, these findings highlight that CMTM6 plays an important role in the tumor immune microenvironment, and CMTM6 has been identified to have prognostic value in some types of cancers. Thus, CMTM6 is a potential target for cancer immunotherapy and effective prognostic biomarker.

Copyright © 2021 Zhao, Zhang, Pu, Guo, Zhang and Wang.

In plain English

This study did not examine asbestos exposure. It was a computer-based analysis of public cancer databases. It asked whether the activity level of a gene called CMTM6 in tumors related to the immune environment around tumors and to patient survival. The authors used gene-activity data from 11,093 normal and tumor tissue samples covering 33 cancer types in The Cancer Genome Atlas, splitting patients into high and low CMTM6 groups at the median value, and added data from other public databases. Mesothelioma was one of the 33 cancer types. The article does not say how many mesothelioma patients were included or whether their tumors were pleural or peritoneal. In the results section, high CMTM6 was linked to worse overall survival in mesothelioma (p = 0.048), adrenocortical carcinoma, lower grade glioma and pancreatic adenocarcinoma, but not in 29 other cancer types. The article's abstract and discussion give a different list of cancers, although mesothelioma appears in both lists. The authors concluded that high CMTM6 was associated with immune checkpoint gene expression and poor prognosis. They said further in vitro, ex vivo and in vivo studies are needed to support their findings.

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: Bioinformatic (database) analysis of publicly available cancer genomic and protein data across many cancer types (pan-cancer); survival compared by Kaplan-Meier method and log-rank tests
• Who was studied: 11,093 normal and tumor tissue samples covering 33 cancer types from The Cancer Genome Atlas (TCGA), including mesothelioma (number of mesothelioma cases and tumor site not given); plus Human Protein Atlas and The Cancer Proteome Atlas (6,944 tumor samples, 32 cancer types) data
• Exposure: No asbestos or occupational exposure was studied. The factor studied was tumor CMTM6 gene expression, with patients divided into high and low expression groups at the median value
• Main results:
  • In the results section, high CMTM6 expression was an unfavorable factor for overall survival in adrenocortical carcinoma (p = 0.0023), lower grade glioma (p < 0.001), mesothelioma (p = 0.048) and pancreatic adenocarcinoma (p = 0.0036)
  • High CMTM6 expression was not associated with prognosis in 29 other cancer types
  • The discussion gives a different list of cancers in which high CMTM6 was associated with poor prognosis: adrenocortical carcinoma, glioblastoma multiforme, acute myeloid leukemia, liver hepatocellular carcinoma, mesothelioma, sarcoma, thymoma and uveal melanoma
  • CMTM6 mutation frequencies were low across cancers and highest in uterine cancer. Among the 9,477 samples, amplification accounted for 0.49% (46/9,477) and insertions and deletions for 0.32% (30/9,477)
  • High CMTM6 expression was positively associated with neutrophil infiltration in 14 cancer types
  • CMTM6 mRNA expression was associated with PD-L1 protein expression in nine cancer types; mesothelioma was not among them
• The authors' conclusion: The authors concluded that CMTM6 is expressed differently across cancers, and that high CMTM6 expression was associated with expression of immune checkpoint-associated genes and with poor prognosis in several cancers
• Limitations the authors state:
  • The authors stated that ex vivo and in vivo studies are required to support their findings
  • The authors stated that the link between CMTM6 and neutrophils needs validation in further in vitro and in vivo research

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Immunotherapy, Microsatellite Instability (MSI-H), Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma, Sarcoma, Overall Survival.

Related studies

• Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications — S. Ge, Y. Zhao, et al. (2024)
• Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy — J. Harber, T. Kamata, et al. (2021)
• Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients — N. Fusco, V. Vaira, et al. (2020)
• Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma — H. Ollila, M.I. Mäyränpää, et al. (2022)
• Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma — A.N. Qualiotto, C.M. Baldavira, et al. (2023)
• Dynamic evolution of NK cells and immune remodeling mediated by CRS + HIPEC: prognostic mechanisms and therapeutic implications for malignant peritoneal mesothelioma — Y.T. Liu, Q.D. Zhao, et al. (2025)

Browse more research in Frontiers in Oncology, or return to medical research.