Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 31:9:769032.
doi: 10.3389/fmolb.2022.769032. eCollection 2022.

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

Bo Yin  1 , Jianyi Ding  1 , Haoran Hu  1 , Meiqin Yang  1 , Baoyou Huang  1 , Wei Dong  1 , Fang Li  2 , Lingfei Han  1
Affiliations

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

Bo Yin et al. Front Mol Biosci. .

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.

Keywords: CMTM6; biomarker; immunity; ovarian cancer; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
High expression of CMTM6 in various cancers and OV. (A) mRNA level of CMTM6 in human cancer tissues and corresponding normal tissues from GEPIA2. The expression of CMTM6 in the OV samples derived from the Oncomine database. Data shown for (B) ovarian endometrioid adenocarcinoma, (C) ovarian serous adenocarcinoma, (D) ovarian clear cell adenocarcinoma, (E) ovarian mucinous adenocarcinoma, and (F) ovarian carcinoma. (G) CMTM6 expression in OV matched TCGA and GTEx data. (H) Representative immunohistochemistry images and detailed information on the expression of CMTM6 in OV tissues and non-tumor tissues based on the THPA database. ***P < 0.001.
FIGURE 2
FIGURE 2
CMTM6 expression in OV cell lines. (A) Cell line indicated by the red arrow is ovarian cancer. CMTM6 was overexpressed in OV cell lines. (B) CMTM6 mRNA expression in human OV cell lines. (C,D) CMTM6 protein expression in human cell lines. Densitometric quantification was shown. Actin served as the loading control. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.
FIGURE 3
FIGURE 3
Prognostic value of CMTM6 expression and ROC analysis. (A,B) Survival analysis of CMTM6 in OV showed that high CMTM6 expression has an increased OS and DFS based on TCGA database. (C) ROC curve indicated the better performance of survival prediction. (D) Forest plot showed the correlation between CMTM6 expression and clinicopathological parameters in OV patients.
FIGURE 4
FIGURE 4
Enrichment plots from the GSEA. GSEA results showing (A) natural killer cell–mediated cytotoxicity, (B) chemokine signaling pathway, (C) B cell receptor signaling pathway, (D) T cell receptor signaling pathway, (E) apoptosis, and (F) cell cycle.
FIGURE 5
FIGURE 5
First 100 genes coexpressed with CMTM6 in OV were screened from Tothill Ovarian in the Oncomine database.
FIGURE 6
FIGURE 6
PPI network and GO/KEGG enrichment analysis of genes coexpressed with CMTM6. (A) PPI network of genes coexpressed with CMTM6 constructed in the GeneMANIA database. (B) Visualization of a GeneMANIA-derived network complex of molecular interactions in Cytoscape pathway visualization. (C,D) Enriched GO terms in the “biological process” and enriched GO terms in the “cellular component”; the top 10 are displayed. (E) KEGG pathway annotations. The X-axis represented the proportion of coexpressed genes, and the Y-axis represented different categories. The different colors indicate different properties, and the different sizes represent the number of genes.
FIGURE 7
FIGURE 7
CMTM6 expression was associated with immune infiltration in OV from the TISIDB database. (A–D) Spearman relations between the abundances of TILs (A), immunoinhibitors (B), immunostimulators (C), and MHC molecules (D); the top 2 are exhibited. The relationship of CMTM6 expression with (E–I) chemokines and (J) chemokine receptor.
FIGURE 8
FIGURE 8
Kaplan–Meier survival curve comparison of the high and low expression of corresponding chemokines and chemokine receptor in GSE26193. (A–C) High CCL20, CXCL5, and CXCL8 had better survival in OV. (D) Relationship between CXCL11 expression and survival in OV. (E) Overexpressed CXCL16 had longer survival in OV. (F) Relationship between CXCR4 expression and survival in OV (p < 0.05).
FIGURE 9
FIGURE 9
CNV, methylation, and mutation analysis of CMTM6 in OV (UCSC Xena and cBioPortal). (A) Heatmap viewing the associations between CMTM6 mRNA and CNV, methylation, and somatic mutations in OV. (B,C) Summary of genetic alteration feature of CMTM6 within OV. CMTM6 was altered in four samples of 1,680 samples with OV (2.3%). (D) Relation of CMTM6 expression and the methylation level for OV.
See this image and copyright information in PMC

References

    1. Azimi F., Scolyer R. A., Rumcheva P., Moncrieff M., Murali R., McCarthy S. W., et al. (2012). Tumor-infiltrating Lymphocyte Grade Is an Independent Predictor of sentinel Lymph Node Status and Survival in Patients with Cutaneous Melanoma. Jco 30 (21), 2678–2683. 10.1200/JCO.2011.37.8539 - DOI - PubMed
    1. Barretina J., Caponigro G., Stransky N., Venkatesan K., Margolin A. A., Kim S., et al. (2012). The Cancer Cell Line Encyclopedia Enables Predictive Modelling of Anticancer Drug Sensitivity. Nature 483 (7391), 603–607. 10.1038/nature11003 - DOI - PMC - PubMed
    1. Bedognetti D., Hendrickx W., Ceccarelli M., Miller L. D., Seliger B. (2016). Disentangling the Relationship between Tumor Genetic Programs and Immune Responsiveness. Curr. Opin. Immunol. 39, 150–158. 10.1016/j.coi.2016.02.001 - DOI - PubMed
    1. Block M. S., Dietz A. B., Gustafson M. P., Kalli K. R., Erskine C. L., Youssef B., et al. (2020). Th17-inducing Autologous Dendritic Cell Vaccination Promotes Antigen-specific Cellular and Humoral Immunity in Ovarian Cancer Patients. Nat. Commun. 11 (1), 5173. 10.1038/s41467-020-18962-z - DOI - PMC - PubMed
    1. Burr M. L., Sparbier C. E., Chan Y. C., Williamson J. C., Woods K., Beavis P. A., et al. (2017). CMTM6 Maintains the Expression of PD-L1 and Regulates Anti-tumour Immunity. Nature 549 (7670), 101–105. 10.1038/nature23643 - DOI - PMC - PubMed

LinkOut - more resources