Bioinformatics-Based Discovery of CKLF-Like MARVEL Transmembrane Member 5 as a Novel Biomarker for Breast Cancer.

Juan Zhou,San-Gang Wu,Zhen-Yu He,Jian Lei,Jun Wang,Chen-Lu Lian,Li Hua

doi:10.3389/fcell.2019.00361

Abstract

Chemokine-like factor (CKLF)-like MARVEL transmembrane members (CMTMs) represent a novel protein family linking the chemokine and transmembrane-4 superfamily families, which potentially play several roles in diverse physiological and pathological processes. The detailed functions and underlying molecular mechanisms of CMTMs remain elusive in breast cancer. Herein, we performed a comprehensive bioinformatic analysis to investigate the prognostic effect, potential functions, and biomolecular regulatory network of CMTMs in breast cancer. The mRNA expression level of CMTM5, in particular, was significantly downregulated in breast cancer; moreover, high mRNA expression level of CMTM5 was significantly associated with better relapse-free survival. DNA promoter hypermethylation of CMTM5 was negatively correlated with its mRNA expression levels. Furthermore, CMTM5 strongly associated with pathway in MARVEL domains, chemotaxis, cytokines, transmembrane structures, and integral component of membrane. For example, genes related to MARVEL domains, transmembrane structures, and chemokines were significantly enriched. Our findings indicate that CMTM5 can be used as a prognostic biomarker and potential therapeutic target for breast cancer.

Highlights

Breast cancer is the most common malignancy in women; approximately 2 million new cases are annually diagnosed worldwide (Ferlay et al, 2015)
The mRNA expression levels of CMTM1, CMTM2, CMTM4, and CMTM5 were significantly downregulated whereas those of CMTM3, CMTM6, and CMTM8 were noticeably upregulated in human tumors than in normal tissues
We found that the expression levels of all CMTM family members were significantly dysregulated in breast cancer tissues

Summary

Introduction

Breast cancer is the most common malignancy in women; approximately 2 million new cases are annually diagnosed worldwide (Ferlay et al, 2015). In 2005, chemokine-like factor superfamily members 1–8 (CKLFSF1–8) were renamed CKLF-like MARVEL transmembrane domain-containing 1–8 (CMTM1–8). CKLF and CMTM1–8 represent a novel protein family linking the chemokine and transmembrane-4 superfamily (TM4SF) families, which potentially play several roles in diverse physiological and pathological processes (Han et al, 2003). CMTM family members play a key role in the immune system, tumorigenesis, and male reproductive system (Lu et al, 2016). Little remains known regarding the function of CMTM family members in breast cancer development and progression

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