High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients

Abstract

High-level expression of Rad51, a key factor in homologous recombination, has been observed in a variety of human malignancies. This study was aimed to evaluate Rad51 expression to serve as prognostic marker in non-small-cell lung cancer (NSCLC). A total of 383 non-small-cell lung tumours were analysed immunohistochemically on NSCLC tissue microarrays. High-level Rad51 expression was observed in 29.4% (100 out of 340) of cases. Patients whose tumours displayed high-level Rad51 expression showed a significantly shorter median survival time of 19 vs 68 months (Po0.0001, log-rank test). Similarly T status, N status, M status, clinical stage and histological tumour grade were significant prognostic markers in univariate Cox survival analysis. Importantly, Rad51 expression (Po0.0001) together with tumour differentiation (Po0.009), clinical stage (P ¼ 0.004) and N status (P ¼ 0.0001) proved to be independent prognostic parameters in multivariate analysis. Rad51 expression predicted the outcome of squamous cell cancer as well as adenocarcinoma of the lung. Our results suggest that Rad51 expression provides additional prognostic information for surgically treated NSCLC patients. We hypothesise that the decreased survival of NSCLC patients with high-level expression of Rad51 is related to an enhanced propensity of tumour cells for survival, antiapoptosis and chemo-/radioresistance.

Structure-Function Relationship of DNA Repair Proteins: Lessons from BRCA1 and RAD51 Studies

“…While no mutations have ever been detected in human cancers, in many tumors significantly up-or downregulated levels of RAD51 have been observed (Maacke et al, 2000;Henning & Sturzbecher 2003;Klein, 2008). Moreover, high-level expression of RAD51 is an independent prognostic marker of survival in non-small-cell lung cancer patients (Qiao et al, 2005). In addition, haematopoietic progenitor cells, when Rad51 is overexpressed showed elevated levels of chromosomal alterations, similar to those observed in tumors of the hematopoietic system (Francis and Richardson, 2007).…”

Effects of Emodin Extracted from Chinese Herbs on Proliferation of Non-small Cell Lung Cancer and Underlying Mechanisms

“…High expression of Rad51 in tumor tissues is associated with an unfavorable prognosis in lung cancer (Qiao et a1., 2005). A report showed that the downregulation of Rad51 in lung cancer cells could increase the chemosensitivity of cells to gemcitabine .…”

Autocrine human GH promotes radioresistance in mammary and endometrial carcinoma cells

“…We observed increased RAD51 protein levels in MDA-hGH vs MDA-vector cell lines and T47D-hGH vs T47D-vec cell lines (Supplementary Figure 1, see section on supplementary data given at the end of this article). RAD51 overexpression has been demonstrated in numerous human tumour cell lines and primary tumour samples (Xia et al 1997, Ohnishi et al 1998, Maacke et al 2000a,b, Collis et al 2001, Raderschall et al 2002, Qiao et al 2005, Richardson 2005 and has been linked to reduced sensitivity to IR in numerous cell types, including breast cancer (Maacke et al 2000b, Russo et al 2008, Le Scodan et al 2010, prostate cancer (Collis et al 2001) and glioma (Ohnishi et al 1998). Elevated levels of RAD51 in breast cancer samples correlate with increased invasiveness and poor outcome in patients (Maacke et al 2000b, Russo et al 2008, Le Scodan et al 2010).…”