Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

Abstract

Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

“…PARP-1 expression has been previously demonstrated to be associated with the poor prognosis of numerous tumor types, including early breast cancer and non-small cell lung cancer (13,40–42). However, Aiad et al (43) demonstrated that high nuclear PARP-1 expression levels were significantly associated with improved OS in locally advanced breast cancer; Klauschen et al (44) demonstrated that low nuclear expression levels of PARP were associated with a poor prognosis in pancreatic cancer.…”

Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen

“…Lung cancer, the leading cause of cancer-related deaths, is one of the most common malignant tumors around the world, of which incidence and mortality have massive growth every year as a result of environmental pollution, excessive cigarette smoking, and second-hand smoke [1]. Importantly, nonsmall-cell lung cancer (NSCLC) is considered to be the major type of lung cancers which occupy approximately 85 % of all lung malignant neoplasms, and the 5-year survival rate remained about 15 % and still has not been increased during the last 30 years [2].…”

Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

“…Nucleotide excision repair (NER) and base excision repair (BER) pathway are major DNA repair systems. Besides XRCC1, other DNA base excision repair genes including OGG1, [17] APE1, [17, 39–41] XRCC3, [42] PARP1, [43] were reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen. Genes involved in NER system such as ERCC1 [41, 43–45], ERCC2(XPD), [44, 46] BAG1, [46] XPA, [47] were also reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen.…”