Expression and Clinical Significance of CMTM6 in Hepatocellular Carcinoma

Zhu, Xiaonian; Qi, Guangzi; Liu, Cong; Bei, Chunhua; Tan, Chao; Zhang, Ying; Shi, Wenxiang; Zeng, Wen; Kong, Juan; Fu, Yuanyuan; Tan, Shengkui

doi:10.1089/dna.2018.4513

Cited by 55 publications

(43 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17,18 CMTM6 is involved in the DNA methylation of hepatocellular carcinoma 19 and CMTM6 overexpression is associated with prognosis in glioma 20 and hepatocellular carcinoma. 21 Recently, two studies reported that CMTM6 regulated antitumor immunity by maintaining the expression of PD-L1. 11,12 Mezzadra et al reported that CMTM6 was associated with PD-L1 protein.…”

Section: Discussionmentioning

confidence: 99%

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

et al. 2019

View full text Add to dashboard Cite

CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6 in non-small cell lung cancer (NSCLC) and its association with PD-L1 has not been confirmed. The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles for anti-PD-1 therapy in non-small cell lung cancer. CMTM6 and PD-L1 immunohistochemical expressions were evaluated in 35 advanced, treatment-refractory NSCLC patients who received PD-1 inhibitor therapy. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (Pearson's r = 0.342 and p = .044). A positive correlation was also identified in the mRNA expression data. Using receiver operating characteristic curves, the levels of CMTM6 and PD-L1 expression which provided the best distinguishing point between responder versus non-responder to PD-1 inhibitors were 70 and 75 H-scores, respectively. The patients in the PD-1 inhibitor responder group had higher CMTM6 expressions in univariate logistic regression analysis (odds ratio (OR) = 5.333, p = .037). However, PD-L1 expression was not associated with response to PD-1 inhibitor (p = .288). In multivariate analysis, CMTM6 was also found to be an independent predictor of the response to PD-1 inhibitors (OR = 6.226, p = .032). CMTM6 expression can be a promising predictor useful for therapeutic decision-making regarding PD-1 inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Accumulated evidences have shown that CMTM members play a critical role in cancer development and progression [4][5][6]. Our previous studies also have found that CMTM4, CMTM6, and CMTM7 were downregulated in HCC tissues by immunohistochemistry, and had a relationship with the poor prognosis of HCC patients after survival analysis, suggesting a tumor suppressor role of CMTM members in HCC carcinogenesis and progression [7][8][9].…”

Section: Introductionmentioning

confidence: 77%

Down-regulated CMTM7 promotes metastasis of hepatocellular carcinoma via its family member CMTM3

Zhu¹,

Bei²,

Di³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background Human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) members are found deregulated in various cancers and play a role in cancer development. Recent studies showed that CMTM7 was down-regulated in liver cancer and functioned as a tumor suppressor. Methods The expression of CMTM7 in hepatocellular carcinoma (HCC) tissues was measured by bioinformatics analysis, Western blot, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). CCK8 and cell colony formation assays were conducted to detect the cell proliferation. Cell invasion and migration ability was assessed by wound healing and Transwell assays. Results We identified a decreased expression of CMTM7 in HCC tissues was closely related to the metastasis and prognosis of HCC patients. To explore the effect of CMTM7 on the biological function of HCC cells, we over-expressed CMTM7 in two HCC cell lines, SK-Hep-1 and Bel-7402 cells. Cell proliferation was reduced significantly after exogenous expression of CMTM7, detected by both CCK8 and colony formation assay. Moreover, the invasion and migration ability of HCC cells were also inhibited by exogenous expression of CMTM7 in wound healing and Transwell assay. Furthermore, there was a significantly positive correlation between CMTM7 and CMTM3 both in HCC cells and tumor tissues. Conclusions Our results suggest that down-regulated CMTM7 promotes metastasis of HCC through inducing the expression of its family member CMTM3.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Expression and Clinical Significance of CMTM6 in Hepatocellular Carcinoma

Cited by 55 publications

References 23 publications

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

Down-regulated CMTM7 promotes metastasis of hepatocellular carcinoma via its family member CMTM3

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

Contact Info

Product

Resources

About