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":"ERCC1和ERCC2表达的遗传特征，以及snp变异，揭示了接受铂类化疗的SCLC患者的良好预后。","authors":"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","doi":"10.32604/or.2024.050161","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The comprehensive analysis of <i>ERCC</i> gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 1","pages":"45-55"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671403/pdf/","citationCount":"0","resultStr":"{\"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.\",\"authors\":\"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\",\"doi\":\"10.32604/or.2024.050161\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The comprehensive analysis of <i>ERCC</i> gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.</p>\",\"PeriodicalId\":19537,\"journal\":{\"name\":\"Oncology Research\",\"volume\":\"33 1\",\"pages\":\"45-55\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671403/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncology Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.32604/or.2024.050161\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.32604/or.2024.050161","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：铂化疗（CT）仍然是小细胞肺癌（SCLC）患者全身治疗的支柱。核苷酸切除修复（NER）途径在铂类药物对DNA损伤的修复中起核心作用。这种修复机制的改变可能会影响患者的生存。材料和方法：我们对2015年至2020年在意大利佛罗伦萨Careggi大学医院临床肿瘤科接受铂ct检查的38例广泛疾病(ED)-SCLC患者的数据进行了回顾性分析。对患者肿瘤样本进行三种NER通路基因ERCC1、ERCC2和ercc5的mRNA表达分析和单核苷酸多态性（SNP）表征。结果：总体而言，与健康对照组相比，SCLC患者中ERCC基因的表达升高。ERCC1和ERCC5低表达水平的患者表现出更好的中位无进展生存期（mPFS = 7.1 vs. 4.9个月，ERCC1 = 0.39, mPFS = 6.9 vs. 4.8个月，ERCC5 = 0.093）和总生存期（mOS = 8.7 vs. 6.0个月，ERCC1 = 0.4, mOS = 7.2 vs. 6.2个月，ERCC5 = 0.13）。ERCC基因的5个SNP基因分型分析显示，携带ERCC1 rs11615 SNP的野生型或杂合变体（PFS为p = 0.24， OS为p = 0.14）以及rs13181和rs1799793 ERCC2 SNP （PFS为p = 0.43和p = 0.26， OS为p = 0.21和p = 0.16）的患者的生存期比纯合突变型患者更长。结论：ERCC基因表达和SNP变异的综合分析似乎确定了从铂ct中获得更大生存益处的患者。
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.
期刊介绍：
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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