Genetic signatures of ERCC1 and ERCC2 expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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 damage exerted by platinum agents. Alteration in this repair mechanism may affect patients’ survival. Materials and Methods: We conducted a retrospective analysis of data from 38 patients with extensive disease (ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), from 2015 to 2020. mRNA expression analysis and single nucleotide polymorphism (SNP) characterization of three NER pathway genes—namely ERCC1, ERCC2, and ERCC5—were performed on patient tumor samples. Results: Overall, elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls. Patients with low ERCC1 and ERCC5 expression levels exhibited 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 comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.