与单核苷酸多态性（SNPs）变异一起，[具体基因名称1]和[具体基因名称2]表达的遗传特征揭示了接受铂类化疗的小细胞肺癌（SCLC）患者的良好预后。（注：原文中“and expression”前缺少具体基因名称，这里用[具体基因名称1]和[具体基因名称2]代替以便完整表意）

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

作者信息

Caliman Enrico, Fancelli Sara, Scolari Federico, Pasqui Adriano, Manneschi Clara, Lavacchi Daniele, Mazzoni Francesca, Gensini Francesca, Pasini Valeria, Comin Camilla Eva, Voltolini Luca, Pillozzi Serena, Antonuzzo Lorenzo

机构信息

Clinical Oncology Unit, Careggi University Hospital, Florence, 50134, Italy.

Department of Experimental and Clinical Medicine, University of Florence, Florence, 50134, Italy.

出版信息

Oncol Res. 2024 Dec 20;33(1):45-55. doi: 10.32604/or.2024.050161. eCollection 2025.

DOI:10.32604/or.2024.050161

PMID:39735668

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11671403/

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 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.

摘要

背景

铂类化疗（CT）仍然是小细胞肺癌（SCLC）患者全身治疗的主要方法。核苷酸切除修复（NER）途径在铂类药物所致DNA损伤的修复中起核心作用。这种修复机制的改变可能影响患者的生存。

材料与方法

我们对2015年至2020年在意大利佛罗伦萨卡雷吉大学医院临床肿瘤科接受铂类CT治疗的38例广泛期疾病（ED）-SCLC患者的数据进行了回顾性分析。对患者肿瘤样本进行了三个NER途径基因（即、和）的mRNA表达分析和单核苷酸多态性（SNP）特征分析。

结果

总体而言，与健康对照相比，SCLC患者中基因表达升高。表达水平低的患者表现出更好的中位无进展生存期（mPFS = 7.1对4.9个月，时 = 0.39，mPFS = 6.9对4.8个月，时 = 0.093）和总生存期（mOS = 8.7对6.0个月，时 = 0.4，mOS = 7.2对6.2个月，时 = 0.13）。对基因的五个SNP进行基因分型分析显示，与纯合突变基因型患者相比，携带rs11615 SNP野生型基因型或杂合变异的患者生存期更长（PFS时 = 0.24，OS时 = 0.14），rs13181和rs1799793 SNP的患者也是如此（PFS时 = 0.43和 = 0.26，OS时 = 0.21和 = 0.16）。