Zhu Xuan, Chen Huihui, Yang Yi, Xu Chunjing, Zhou Jun, Zhou Jiaojiao, Chen Yiding
Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China,
The 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,
Cancer Manag Res. 2018 Dec 5;10:6649-6668. doi: 10.2147/CMAR.S185769. eCollection 2018.
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.
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.
Increased expression of 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 mRNA was correlated with reduced distant metastasis-free survival (DMFS) in all patients. Increased expression of mRNA was associated with improved OS and RFS in breast cancer patients. Increased expression of 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 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.
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.
五种RecQ解旋酶家族成员在维持基因组稳定性方面发挥作用。然而,它们在乳腺癌中的预后作用仍不清楚。我们旨在研究RecQ家族的预后价值及乳腺癌的临床结局。
我们使用Kaplan-Meier Plotter数据库(http://kmplot.com/analysis)分析RecQ家族mRNA表达在所有乳腺癌、不同内在亚型及临床病理特征中的预后价值。通过免疫组织化学(IHC)在乳腺癌组织中证实WRN和RECQL4的蛋白表达水平。
在所有乳腺癌中,mRNA表达增加与无复发生存期(RFS)和进展后生存期(PPS)降低显著相关,而在基底样乳腺癌患者和p53突变型乳腺癌患者中与总生存期(OS)改善相关。在所有患者中,mRNA表达增加与无远处转移生存期(DMFS)降低相关。在乳腺癌患者中,mRNA表达增加与OS和RFS改善相关。在所有乳腺癌中,mRNA表达增加与OS、DMFS和RFS降低相关,在腔面A型、HER2阳性、雌激素受体(ER)阳性和孕激素受体(PR)阳性乳腺癌患者中与OS降低相关。在所有患者中,mRNA表达增加与RFS改善相关,在淋巴结阴性乳腺癌患者中与OS改善相关,但在HER2阳性乳腺癌患者中与OS降低相关。免疫组织化学染色证实,在蛋白水平上,WRN高表达与OS增加相关,RECQL4高表达与OS降低相关。
RecQ成员的mRNA表达水平与乳腺癌患者的预后显著相关。这些初步发现需要进一步研究,以确定是否可以开发针对RecQ的试剂用于乳腺癌的临床应用。