ERCC1 and ERCC2 genes expression and their SNPs variants identify a favorable signature for SCLC patients treated with platinum-based chemotherapy

Abstract

Abstract Background: Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damages exerted by platinum agents. Alteration in this repair mechanism may affect patients survival. Methods: We retrospectively collected data from 38 patients with extended disease (ED)-SCLC treated with platinum-CT at Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), between 2015 to 2020. On patient tumor samples, we performed mRNA expression analysis and characterization of single nucleotide polymorphisms (SNPs) of three NER pathway genes, namely ERCC1, ERCC2 and ERCC5. Results: Overall, we found a higher expression of ERCC genes in SCLC patients compared to the healthy controls. Patients with low ERCC1 and ERCC5 expression levels had a better median progression free survival (mPFS=7.1 vs 4.9 months, p=0.39 for ERCC1 and mPFS=6.9 vs 4.8 months, p=0.093 for ERCC5) and overall survival (mOS=8.7 vs 6.0 months, p=0.4 for ERCC1 and mOS=7.2 vs 6.2 months, p=0.13 for ERCC5). Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP (p=0.24 for PFS and p=0.14 for OS) and of the rs13181 and rs1799793 ERCC2 SNPs (p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS, respectively) compared to patients with homozygous mutant genotypes. Conclusions: The integrated analysis of ERCC genes expression and their SNPs variants seems to identify patients with better survival benefits to platinum-CT.