DNAJC9 expression in basal-like and luminal A breast cancer subtypes predicts worse survival

Abstract

Background: This study aimed to analyze the role of genetic/epigenetic alterations and the prognostic value of the DNAJC9 gene in breast cancer.

Materials and methods: RT-PCR and Q-RT-PCR methods are used to examine DNAJC9 expression in breast cell lines. Survival ratios of breast cancer patients were evaluated by using bc-GenExMiner. Combined bisulfite restriction analysis and UALCAN in-silico tool were used to assess the methylation level of the DNAJC9 promoter. Mutations were searched with the help of Sanger Cosmic database and direct sequencing.

Results: DNAJC9 mRNA expression is significantly higher in basal-like, HER2-Enriched (HER2-E), luminal A and luminal B breast cancer subtypes compared to normal breast-like samples based on DNA microarray datasets (P < 0.001). Similar results were obtained in RNA-seq datasets, except for the luminal A breast cancer subtype (P > 0.1). We did not find any mutation at the core promoter region of DNAJC9 in breast cancer and normal cell lines. Mutations of DNAJC9 are infrequent in clinical samples (<%1). DNAJC9 promoter region is hypomethylated in tumor and normal samples. DNAJC9 expression is unfavorable for survival in basal-like and luminal A breast cancer subtypes.

Conclusions: Mutations or promoter hypomethylation do not appear to have a role in high DNAJC9 gene expression in breast cancer. DNAJC9 expression could be suggested as a novel biomarker in basal-like and luminal A breast cancer subtypes.

Keywords: Biomarker; Breast cancer; DNAJC9; HSP40.