High DNAJA4 expression correlates with poor survival outcomes in breast cancer

Abstract Background: DNAJA4 (PRO1472) is a heat shock protein that has been associated with several types of cancers, including breast cancer. We aimed to reveal the protein expression, clinical outcomes, and regulatory mechanisms of DNAJA4 gene in breast cancer by employing tissue microarrays, transcriptomic datasets, and in-silico tools. Methods: DNAJA4 protein expression and its clinical implications were evaluated by immunohistochemistry assay (normals = 32; tumors = 121). RNA-seq and DNA microarray datasets were analyzed by using breast cancer gene-expression miner (Bc-GenExMiner v4.8) to estimate the survival probabilities of breast cancer patients. DNAJA4 promoter methylation level was analyzed in clinical samples by UALCAN in-silico tool (normals = 97; tumors = 793). Results: DNAJA4 protein expression is significantly high in clinical breast cancer samples compared to the normal samples (P = 0.016). High DNAJA4 mRNA expression is correlated with poor overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) in breast cancer patients (P < 0.05). Mutations or copy number variations of DNAJA4 are uncommon in clinical samples. Reduced promoter methylation was observed in clinical breast cancer samples. Conclusion: We suggest DNAJA4 expression as a new biomarker candidate for breast cancer. Promoter hypomethylation could be an important epigenetic factor in the upregulation of DNAJA4 expression in breast cancer.