Low expression of RECQL is associated with poor prognosis in Chinese breast cancer patients

Abstract

BackgroundRECQL is a number of the RecQ DNA helicase family and plays an important role in maintaining genome stability. Although several studies have reported that RECQL mutations were correlated with the susceptibility to breast cancer, the effect on prognosis in breast cancer was not yet clarified. Here, we explored the association between RECQL expression level and survival in patients with breast cancer.MethodsIn the first cohort, the RECQL mRNA expression level was evaluated in 774 primary breast cancer patients using a quantitative real-time PCR assay. Then, in the second independent cohort, the level of RECQL protein expression was detected in 322 patients with breast cancer using immunohistochemistry assay. Survival curves of patients with RECQL expression were compared using the Kaplan-Meier method with log-rank test.ResultsIn the first cohort of 774 breast cancer patients, the low expression level of RECQL mRNA was significantly correlated with aggressive clinicopathological characteristics, including the positive lymph node status (P = 0.026), HER2 overexpression (P < 0.001), ER negative status (P = 0.047) and high tumor grade (P = 0.041). Moreover, the low expression level of RECQL mRNA was significantly associated with poor distant recurrence-free survival (DRFS, unadjusted hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.88–4.09, P < 0.001) and disease-specific survival (DSS, unadjusted HR: 3.10, 95% CI: 1.84–5.20,P < 0.001), and it remained an independent unfavorable factor for DRFS and DSS (DRFS: adjusted HR: 3.04, 95% CI: 1.89–4.87, P < 0.001; DSS: adjusted HR: 4.25, 95% CI: 2.12–8.46, P < 0.001). In the second cohort of 322 breast cancer patients, low expression of RECQL protein was also subject to poor survival in breast cancer, and it was an independent prognosis factor of poor DRFS by multivariate analysis (DRFS: adjusted HR: 2.12, 95% CI: 1.16–3.88, P = 0.015).ConclusionsBreast cancer patients with low RECQL expression had a worse survival. The expression level of RECQL may be a potential prognosis factor for breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4585-1) contains supplementary material, which is available to authorized users.

High Expression of RECQL Protein in ER-Positive Breast Tumours Is Associated With a Better Survival

“…In a study by Arora et al low RECQL mRNA and protein levels in breast tumours were associated with poor breast cancer prognosis ( 1 ). This correlation was observed in a second study which showed low RECQL protein levels were correlated with poor survival (HR: 2.12, p-value: 0.015) ( 2 ). Furthermore, in a recent study, the cellular mechanism by which RECQL affects ER-positive cells was proposed, wherein RECQL in cooperation with FOXA1, directly regulates the expression of the ESR1 gene which encodes the ERα protein ( 28 ).…”

“…The second study also observed that among 774 breast cancer patients, lower mRNA levels of RECQL were associated with poor distant recurrence-free survival (HR: 2.77, p-value <0.001) and disease-specific survival (HR: 3.10, p-value <0.001). In a cohort of 322 breast cancer patients, low RECQL protein levels correlated with poor survival (HR: 2.12, p-value: 0.015); however, the authors did not compare this association among ER-positive versus ER- individuals ( 2 ). These studies also showed that lower RECQL protein levels were associated with poor clinicopathological characteristics ( 1 , 2 ).…”

“…In a cohort of 322 breast cancer patients, low RECQL protein levels correlated with poor survival (HR: 2.12, p-value: 0.015); however, the authors did not compare this association among ER-positive versus ER- individuals ( 2 ). These studies also showed that lower RECQL protein levels were associated with poor clinicopathological characteristics ( 1 , 2 ). We also observed that medium/low RECQL levels were associated with poor clinicopathological characteristics, such as a higher proportion of lymph node-positive tumours (56.1% vs. 47.9%, p-value= 0.05) and larger tumour sizes (27.3 vs 24.2, p-value= 0.01).…”

“…Three other studies have investigated the association between RECQL protein or mRNA levels and breast cancer survival ( 1 , 2 , 34 ). The first study showed that in separate cohorts of 848 and 1977 breast cancer patients, lower protein and mRNA levels of RECQL were associated with worse prognosis; further analysis revealed that this association only held among the ER-positive patients ( 1 ).…”

“…Altered expression levels of several genes in breast cancer predict patient prognosis. A correlation has been observed between poor breast cancer prognosis and lower levels of RECQL (also known as RECQ1 and RECQL1) mRNA or RECQL protein expression ( 1 , 2 ). RECQL is the smallest and most abundant member of the RecQ family of DNA helicases ( 3 , 4 ).…”