Distinct prognosis of mRNA expression of the five RecQ DNA-helicase family members – RECQL, BLM, WRN, RECQL4, and RECQL5 – in patients with breast cancer

Xuan Zhu,1,2,* Huihui Chen,1,* Yi Yang,1,3 Chunjing Xu,1,2 Jun Zhou,4 Jiaojiao Zhou,1,2 Yiding Chen1,2 1Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Breast Surgery, Jiaxing Maternity and Child Health Care Hospital, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Breast Surgery, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Background: Five RecQ helicase family members have a role in maintaining genome stability. However, their prognostic roles in breast cancer remain unknown. We aimed to investigate the prognostic values of the RecQ family and clinical outcomes in breast cancer. Methods: We used the Kaplan–Meier Plotter database (http://kmplot.com/analysis) to analyze prognostic values of RecQ-family mRNA expression in all breast cancers and in different intrinsic subtypes and clinicopathological characteristics. Protein-expression levels of WRN and RECQL4 were confirmed by immunohistochemistry (IHC) in breast cancer tissues. Results: Increased expression of RECQL mRNA was significantly associated with reduced relapse-free survival (RFS) and postprogression survival (PPS) in all breast cancers, and improved overall survival (OS) in patients with basal-like breast cancer and in mutant-p53-type breast cancer patients. Increased expression of BLM mRNA was correlated with reduced distant metastasis-free survival (DMFS) in all patients. Increased expression of WRN mRNA was associated with improved OS and RFS in breast cancer patients. Increased expression of RECQL4 mRNA was associated with reduced OS, DMFS, and RFS in all breast cancers, and with reduced OS in patients with luminal A, HER2-positive, ER-positive, and PR-positive breast cancer. Increased expression of RECQL5 mRNA was associated with improved RFS in all patients, and with improved OS in patients with lymph-node-negative breast cancer, but with reduced OS in patients with HER2-positive breast cancer. IHC staining confirmed that high expression of WRN was correlated with increased OS and high expression of RECQL4 associated with reduced OS at protein levels. Conclusion: mRNA-expression levels of RecQ members were significantly correlated with prognosis in breast cancer patients. These preliminary findings require further study to determine whether RecQ-targeting reagents might be developed for clinical application in breast cancer. Keywords: breast cancer, prognosis, RecQ helicase family, DNA helicase, overall survival, KM plotte