J Cancer 2020; 11(7):1846-1858. doi:10.7150/jca.37247 This issue
1. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China 325027
2. School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China 310015
3. Department of Tumor Biomarker Development, Sino-American Cancer Foundation, Covina, CA, USA 91722
Purpose: DDX39 is a DEAD-box RNA helicase that unwinds double-stranded RNA in an ATP-dependent manner. This study evaluated the prognostic and predictive significance of DDX39 in breast cancer (BC).
Methods: The cellular proliferation, invasion, and drug cytotoxicity by DDX39 siRNA were evaluated in MCF7 (ER-positive) and MDA-MB-231 (ER-negative) cell lines. A total of 27 datasets (total 8110 accessible cases) with following-up information were collected from Asia, Europe, and North America to explore associations between DDX39 gene expression and clinical parameters of BC patients.
Results: Down-regulation of DDX39 by siRNA significantly reduce the cell growth and invasion ability in MCF7 cells, but only slightly in MDA-MB-231 cells. The DDX39 mRNA level was elevated in breast adenocarcinoma compared with normal breast tissue (p<0.01). Higher DDX39 level was significantly correlated with larger tumor size (p<0.01) and poorer tumor differentiation (p<0.01). The prognostic significance of DDX39 for BC was assessed by pooled-analysis and meta-analysis. Kaplan-Meier analysis demonstrated that increased DDX39 mRNA expression was associated with poor outcomes significantly in a dose-dependent manner in ER-positive BC. The prognostic performance of DDX39 mRNA was comparable to 21-gene, 70-gene, and wound-response gene signatures, and it was superior to the TNM stage. Lower DDX39 expression was associated with reduced relative risk death on ER-positive BC with chemotherapy or radiotherapy. Inhibition of DDX39 by siRNA could significantly enhance the sensitivity of MCF-7 to doxorubicin.
Conclusion: DDX39 may be a potential novel prognostic and predictive biomarker for BC patients with ER-positive status.
Keywords: DEAD-box helicase 39 (DDX39), breast cancer, prognostic biomarker, chemoresistance, bioinformatics