Dataset Information

Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

ABSTRACT: Ovarian cancer (OV) is an epithelial malignancy that intrigues people for its high mortality and lack of efficient treatment. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) can be observed in various cancers, but its part in OV remains little known. Hence, the prognostic value and underlying mechanism of CMTM6 in OV were preliminarily evaluated. Here, we determined that CMTM6 expression was higher than that in normal controls. However, the upregulation of CMTM6 was associated with better prognosis. GSEA results suggested that CMTM6 is involved in the immune-related and metabolism-related pathways. GO/KEGG analysis of CMTM6 coexpressed genes was performed to survey the possible regulatory roles of CMTM6 in OV. Subsequently, CMTM6 expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, CMTM6 may influence prognosis partially by regulating immune infiltration in OV. Last, copy number variations (CNVs) and DNA methylation might prompt the abnormal CMTM6 expression in OV. In conclusion, CMTM6 can serve as a novel prognostic biomarker in patients with OV.

SUBMITTER: Yin B

PROVIDER: S-EPMC8841687 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

Yin Bo B Ding Jianyi J Hu Haoran H Yang Meiqin M Huang Baoyou B Dong Wei W Li Fang F Han Lingfei L

Frontiers in molecular biosciences 20220131

Ovarian cancer (OV) is an epithelial malignancy that intrigues people for its high mortality and lack of efficient treatment. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) can be observed in various cancers, but its part in OV remains little known. Hence, the prognostic value and underlying mechanism of CMTM6 in OV were preliminarily evaluated. Here, we determined that CMTM6 expression was higher than that in normal controls. However, the upregulation of CMTM ...[more]

PMID: 35174213

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Project description:BackgroundMore and more evidence suggests that cancer is a mitochondrial metabolic disease recently and mitochondria dysfunction is critical to tumorigenesis. As a gatekeeper of mitochondria, the voltage-dependent anion channel 1 (VDAC1) is associated with the development of breast cancer (BC). However, its potential mechanism and clinical significance remain unclear; thus, in this research, we aimed to explore it.MethodsVDAC1 expression in BC tissues and normal tissues was obtained from The Cancer Genome Atlas (TCGA) and validated by datasets from the gene expression omnibus (GEO) database. Then, the relationships between VDAC1 expression and clinicopathological features were analyzed. Receiver operating characteristics (ROC) curves were used to identify the diagnostic value of VDAC1. The prognostic value was evaluated by Kaplan-Meier survival curves and Cox regression analysis. VDAC1 with its co-expression genes were subjected to enrichment analysis to explore potential mechanisms in BC and the protein-protein interaction (PPI) network was constructed. At last, the association between VDAC1 expression and infiltration levels of immune cell infiltration by various methods, as well as their corresponding markers, was analyzed. We also analyzed the correction between VDAC1 expression and eight immune checkpoint genes and the tumor immune dysfunction and exclusion (TIDE) scores of each BC sample in TCGA were calculated and the differences between high and low VDAC1 expression groups were analyzed.ResultsVDAC1 expression was remarkably elevated in BC (p < 0.001), and high expression of VDAC1 was associated with the positive expression of ER (p = 0.004), PR (p = 0.033), and HER2 (p = 0.001). ROC analysis suggested that VDAC1 had diagnosed value in BC. The Kaplan-Meier analysis suggested that higher expression of VDAC1 was associated with shorter overall survival (OS), and further Cox regression analysis revealed that VDAC1 was an independent factor of unfavorable prognosis in BC patients. Enrichment analysis of VDAC1 and its co-expression suggested that VDAC1 was related to the regulation of mitochondrial energy metabolism and protein modification, and the HIF-1 singing pathway might be the potential mechanism in BC. Notably, we found that VDAC1 expression was infiltration levels of most types of immune cells, as well as the expression of marker genes of immune cells. The ICGs PDCD1, CTLA4, LAG3, SIGLEC15, and TIGIT were negatively corrected with VDAC1 expression in BC. TIDE scores between the low and high expression groups showed no difference.ConclusionOverexpressed VDAC1 in BC could be severed as a novel biomarker for diagnosis and VDAC1 was an independent factor for adverse prognosis prediction. Our study revealed that VDAC1 might inhibit tumor immunity and might be a novel therapeutic target in BC.

Project description:CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a programmed death-ligand 1 (PD-L1) regulator, is widely expressed in various tumors and regulates the immune microenvironment. However, its prognostic value remains controversial, and the roles of CMTM6 in colorectal cancer (CRC) are still unknown. In this study, we aimed to elaborate the expression patterns of CMTM6 and PD-L1 in CRC and investigate their relationship with the infiltration of T cells and the prognosis of patients with CRC. Analysis of CMTM6 mRNA levels, gene ontology enrichment analysis and single-sample gene set enrichment analysis were performed in a The Cancer Genome Atlas colon cancer cohort. The expression of CMTM6 and PD-L1 and the infiltration of T cells in tumor tissues from our cohort containing 156 patients with CRC receiving adjuvant chemotherapy and 77 patients with CRC without chemotherapy were examined by immunohistochemistry assay. CMTM6 expression was upregulated in CRC compared with normal colon tissues, and CMTM6 levels were lower in advanced tumors than in early-stage tumors. High expression of CMTM6 correlated with lower pT stage and more CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and predicted a favorable prognosis in CRC. PD-L1 was expressed in CRC tissues at a low level, and PD-L1 positivity in tumor stroma (PD-L1(TS)), but not PD-L1 positivity in cancer cells (PD-L1(CC)), was associated with an increased density of CD4+ TILs and a favorable prognosis. The coexpression status of CMTM6 and PD-L1(TS) divided patients with CRC into three groups with low, moderate and high risks of progression and death, and patients with CMTM6High/PD-L1(TS)+ status had the longest survival. Moreover, the prognostic value of CMTM6/PD-L1 expression was more significant in patients with CRC treated with adjuvant chemotherapy than in those not treated with chemotherapy. CMTM6 has a critical impact on the immune microenvironment and can be used as an independent prognostic factor for CRC. The coexpression status of CMTM6 and PD-L1 can be used as a new classification to stratify the risk of progression and death for patients with CRC, especially for patients receiving adjuvant chemotherapy. These findings may provide insights into improving responses to immunotherapy-included comprehensive treatment for CRC in the future.

Dataset Information

Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

Publications

Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

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