Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression

Wang, Hui; Gao, Jinping; Zhang, Renfeng; Li, Meng; Peng, Zhongmin; Wang, Haiyong

doi:10.1016/j.intimp.2020.106478

Cited by 35 publications

(33 citation statements)

References 38 publications

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“…Chen et al found that high expression of CMTM6 was associated with low inflammatory density in head and neck squamous cell carcinoma [15]. Wang et al observed that there was a significant correlation between CMTM6 expression and inflammatory cells in lung adenocarcinoma [32]. In our study, we observed that high CMTM6 expression was significantly associated with a high density of inflammatory cells in HCC.…”

Section: Discussionsupporting

confidence: 64%

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Liu

Zhang

Chao

et al. 2020

Cancer Immunol Immunother

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The "macrotrabecular-massive" (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients.

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Section: Discussionsupporting

confidence: 64%

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Liu

Zhang

Chao

et al. 2020

Cancer Immunol Immunother

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“…In lung adenocarcinoma, CMTM6 expression was positively correlated with PD-L1 in both the mRNA and protein levels. Furthermore, CMTM6 expression was positively correlated with immune-in ltrating cells, resting dendritic cells, eosinophils, M1 or M2 macrophages, neutrophils, and CD4 T cells (5). Kan demonstrated that CMTM6 could predict the clinical response to PD-1 inhibitors (6).…”

Section: Discussionmentioning

confidence: 89%

“…To our best knowledge, this is the rst report concerning CMTM6 in GC. Only a few reports have investigated CMTM6 in other solid malignancies (5)(6)(7)(8). In lung adenocarcinoma, CMTM6 expression was positively correlated with PD-L1 in both the mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 99%

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Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

Nishi

Shimada

Yoshikawa

et al. 2020

Preprint

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Background: CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1(PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods: A total of 105 patients who had undergone curative surgical resection for stage II/III GC at Tokushima University Hospital were included in this study. The expression of CMTM and PD-L1 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results: CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS: 57.2% vs. 79.2%, respectively; p<0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS: 52.8% vs. 72.4%, respectively; p=0.20). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p<0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p=0.07), and PD-L1 expression was positively correlated with PD-1 expression (p<0.05).Conclusions: CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC.

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“…Recent studies have shown that CMTM6 plays an oncogenic role and is associated with poor prognosis in gliomas, hepatocellular carcinoma, and LUAD [2,[31][32]. However, there is limited information regarding the prognostic value of CMTM6 in other solid cancer types.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of Pan-cancer CMTM6 Expression and Its Relationship With the Immune Microenvironment

Zhang

Zhao

et al. 2020

Preprint

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Background: 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.Methods: 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.Results: 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. Conclusions: 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 an effective prognostic biomarker.

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Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression

Cited by 35 publications

References 38 publications

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma

Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

Prognostic Implications of Pan-cancer CMTM6 Expression and Its Relationship With the Immune Microenvironment

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