Identification of TMEM178 as a Potential Prognostic Biomarker and Therapeutic Target for Breast Cancer

Jiaoyan  Yan; Ye  Yang; Jingrun  Lu; Yan  Yuan; Xiangyi  Wu; Jian Huang; Shu  Zhang

doi:10.18502/ijph.v52i11.14042

Jiaoyan Yan Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
Ye Yang Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
Jingrun Lu Department of Clinical Laboratory, The First People’s Hospital of Guiyang, Guiyang, 550002, China
Yan Yuan Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
Xiangyi Wu Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
Jian Huang Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
Shu Zhang Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China

DOI: https://doi.org/10.18502/ijph.v52i11.14042

Keywords: Methylation modification; CD4 T subsets; Immunosuppressive molecules

Abstract

Background: The transmembrane protein (TMEM) family plays important roles in cancer. However, the expression pattern and biological roles of TMEM178, a member of TMEM family, remains unclear in breast cancer (BRCA).

Methods: Methylation and RNA-seq data were obtained to explore methylation level. Expression of TMEM178, methylation inhibitor 5-Aza-CdR was used to verify the effect of methylation status on the expression of TMEM178. We comprehensively investigated the prognostic outcomes, biological functions and effects on immune cell infiltration of the TMEM178 in BRCA using multiple bioinformatics methods.

Results: The expression of TMEM178 was downregulated and negatively correlated with the level of DNA methylation and DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) in BRCA. Consistently, TMEM178 mRNA were confirmed to be downregulated, while upregulated in response to treatment with methylation inhibitor 5-Aza-CdR by RT-qPCR. Patients with high expression of TMEM178 have better prognosis and are more sensitive to targeted drug Pazopanib. Immune infiltration analysis showed that the infiltration levels of CD4⁺ T cell subsets were reduced in BRAC tissues with high TMEM178 expression, and immunosuppressive molecules of T-cell exhaustion were lower expression level.

Conclusion: Hypermethylation of the TMEM178 promoter region was a contributing factor to the downregulation of its expression, and TMEM178 may reflect a prognostic and immunosuppressive situation in BRCA.