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

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Oncology research 2025年第1期33卷 45-55页

作者： Enrico Caliman Sara Fancelli Federico Scolari Adriano Pasqui clara manneschi Daniele Lavacchi Francesca Mazzoni Francesca Gensini Valeria Pasini Camilla Eva Comin Luca Voltolini Serena Pillozzi Lorenzo Antonuzzo Clinical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Medicine University of Florence Florence 50134 Italy. Department of Health Sciences University of Florence Florence 50134 Italy. Medical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Biomedical Sciences "Mario Serio" University of Florence Florence 50134 Italy. Section of Anatomic Pathology Department of Health Sciences University of Florence Florence 50139 Italy. Section of Surgery Histopathology and Molecular Pathology University of Florence Florence 50139 Italy. Thoracic Surgery Unit Careggi University Hospital Florence 50134 Italy.

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 , , and -were performed on patient tumor samples.Results:Overall, elevated expression of genes was observed in SCLC patients compared to healthy controls. Patients with low and expression levels exhibited a better median progression-free survival (mPFS = 7.1 . 4.9 months, = 0.39 for and mPFS = 6.9 . 4.8 months, = 0.093 for ) and overall survival (mOS = 8.7 . 6.0 months, = 0.4 for and mOS = 7.2 . 6.2 months, = 0.13 for ). Genotyping analysis of five SNPs of genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the rs11615 SNP ( = 0.24 for PFS and = 0.14 for OS) and of the rs13181 and rs1799793 SNPs ( = 0.43 and = 0.26 for PFS and = 0.21 and = 0.16 for OS, respectively) compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： ERCC genes Nucleotide excision repair (NER) pathway Platinum-chemotherapy (CT) Single nucleotide polymorphisms (SNPs) Small cell lung cancer (SCLC)

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