@Article{or.2024.050161,
AUTHOR = {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},
TITLE = {Genetic signatures of <i>ERCC1</i> and <i>ERCC2</i> expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {1},
PAGES = {45--55},
URL = {http://www.techscience.com/or/v33n1/59093},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> 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. <b>Materials and Methods:</b> 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 <i>ERCC1</i>, <i>ERCC2</i>, and <i>ERCC5</i>—were performed on patient tumor samples. <b>Results:</b> Overall, elevated expression of <i>ERCC</i> genes was observed in SCLC patients compared to healthy controls. Patients with low <i>ERCC1</i> and <i>ERCC5</i> expression levels exhibited a better median progression-free survival (mPFS = 7.1 <i>vs</i>. 4.9 months, <i>p</i> = 0.39 for <i>ERCC1</i> and mPFS = 6.9 <i>vs</i>. 4.8 months, <i>p</i> = 0.093 for <i>ERCC5</i>) and overall survival (mOS = 8.7 <i>vs</i>. 6.0 months, <i>p</i> = 0.4 for <i>ERCC1</i> and mOS = 7.2 <i>vs</i>. 6.2 months, <i>p</i> = 0.13 for <i>ERCC5</i>). Genotyping analysis of five SNPs of <i>ERCC</i> genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the <i>ERCC1</i> rs11615 SNP (<i>p</i> = 0.24 for PFS and <i>p</i> = 0.14 for OS) and of the rs13181 and rs1799793 <i>ERCC2</i> SNPs (<i>p</i> = 0.43 and <i>p</i> = 0.26 for PFS and <i>p</i> = 0.21 and <i>p</i> = 0.16 for OS, respectively) compared to patients with homozygous mutant genotypes. <b>Conclusions:</b> The comprehensive analysis of <i>ERCC</i> gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.},
DOI = {10.32604/or.2024.050161}
}