Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.

BACKGROUND:DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer. METHODS:Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively. RESULTS:DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n = 121) compared with adjacent normal breast tissues (n = 32) (p < 0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n = 626) (p = 0.0096) and relapse-free survival (n = 1764) (p = 5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines. CONCLUSIONS:In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.

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