ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin

Abstract

Background:The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1–3 gene polymorphisms on outcomes of patients was examined.Methods:Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.Results:Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).Conclusion:This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.

Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer

“…Recently, accumulated preclinical and clinical studies have demonstrated that ERCC1 could be as a prognostic factor (information on the patients overall cancer outcome, regardless of therapy), predictive (information on the effect of a therapeutic intervention) and a potential therapeutic target in cancer, including NSCLC (13,17). In these studies, among patients who did not receive chemotherapy, those with ERCC1-positive tumors had longer survival than those with ERCC1-negative tumors (18), however, for the patients with ERCC1-negative tumors, they had a distinctly higher response rate (19) and attained benefit from platinum-based chemotherapy with significantly prolonged survival, but patients with ERCC1-positive tumors did not (18,20,21). In some other studies, inconsistently, ERCC1 expression was not associated with platinum response (22) or survival (23) in NSCLC patients.…”

Study on the ERCC1 gene polymorphism response to chemotherapy and prognosis of gastric cancer

“…Polymorphisms in ERCC1 genes are reported to be a potential predictor for the response to chemotherapy and clinical outcome of cancer patients, such nasopharyngeal carcinoma, colorectal cancer, and non-small cell lung as well as ovarian cancer (Chen et al, 2013;Moxley et al, 2013;Oguri et al, 2013;Tiseo et al, 2013). For gastric cancer, 2 systemic reviews indicated that ERCC1 rs11615C>T polymorphisms are useful prognostic factors in gastric cancer treated with platinum-based chemotherapy (Liu et al, 2011;Wang et al, 2012 Table 3.…”

Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study

“…Tubulin dimers consisting of TUBB3 compose microtubule polymers that interfere with the reaction to paclitaxel by slowing or blocking the transition from metaphase to anaphase in the mitotic cell cycle (15,16). Overall, these capable biomarkers have been demonstrated as prognostic and predictive markers in certain studies, but not in others (17)(18)(19)(20). Accordingly, the present prospective, randomized, non-interventional study was performed to verify the predictive value of the protein expression of ERCC1, BRCA1, RRM1 and TUBB3 in patients with NSCLC that received adjuvant cisplatin-based chemotherapy at the Sun Yat-Sen University Cancer Center (Guangzhou, Guangdong, China).…”