Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers

Abstract

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In this study, we have evaluated RECQL5 mRNA expression in 1977 breast cancers, and RECQL5 protein level in 1902 breast cancers [Nottingham Tenovus series (n = 1650) and ER- cohort (n = 252)]. Expression levels were correlated to aggressive phenotypes and survival outcomes. High RECQL5 mRNA expression was significantly associated with high histological grade (P = 0.007), HER2 overexpression (P = 0.032), ER+/HER2-/high proliferation genefu subtype (P < 0.0001), integrative molecular clusters (intClust 1and 9) (P < 0.0001) and poor survival (P < 0.0001). In subgroup analysis, high RECQL5 mRNA level remains significantly associated with poor BCSS in ER+ cohort (P < 0.0001) but not in ER- cohort (P = 0.116). At the protein level, in tumours with low RAD51, high RECQL5 level was significantly associated with high histological grade (P < 0.0001), higher mitotic index (P = 0.008), dedifferentiation (P = 0.025), pleomorphism (P = 0.027) and poor survival (P = 0.003). In subgroup analysis, high RECQL5/low RAD51 remains significantly associated with poor BCSS in ER+ cohort (P = 0.010), but not in ER- cohort (P = 0.628). In multivariate analysis, high RECQL5 mRNA and high RECQL5/low RAD51 nuclear protein coexpression independently influenced survival (P = 0.022) in whole cohort and in the ER+ subgroup. Preclinically, we show that exogenous expression of RECQL5 in MCF10A cells can drive proliferation supporting an oncogenic function for RECQL5 in breast cancer. We conclude that RECQL5 is a promising biomarker in breast cancer.

Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers

“…An interesting observation was that we did not observe any cytoplasmic staining for RECQL1. This is in contrast to the cytoplasmic staining observed for BLM, RECQL4 and WRN in breast cancers (16, 38, 39). The data suggests differential regulation of localisation for different RecQ helicases.…”

“…We have recently investigated the expression of RECQL4, RECQL5, BLM and WRN in breast cancers (17, 39-41). Whereas high RECQL4, high RECQL5 and high BLM expression were associated with aggressive breast cancers (17, 39, 40), low WRN expression was linked to poor outcomes (41). Interestingly, RecQ helicase mRNA levels are linked to biologically distinct integrative clusters reported in the METABRIC study (15).…”

RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells

“…On the other hand, a large scale expression profiling of RECQL5 in human breast cancer showed that high expression of the helicase is often associated with bad tumor grades and poor prognosis. 38 In line with that, our analysis of RECQL5 expression data also suggests that higher levels of expression are correlated with poorer prognosis of TNBC patients ( Figure 5E). These observations suggest that RECQL5 could also function as an oncogene.…”

Molecular-genetic profiling and high-throughput in vitro drug screening in NUT midline carcinoma—an aggressive and fatal disease

“…However, we were able to identify a recurrent high-impact mutation in the gene RECQL5 , a DNA helicase involved in interstrand crosslinking repair [ 55 , 73 ]. RECQL5 is essential for the maintenance of genomic stability, and polymorphisms in the gene have been associated with both poor prognosis in osteosarcoma and susceptibility to breast cancer [ 61 , 62 , 74 , 75 ]. With deletion of the gene in mice also shown to increase cancer susceptibility, it is clear that RECQL5 is an important tumor suppressor [ 76 , 77 ].…”