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卵巢癌的预后及卡铂反应预测模型:一项基于临床和药物基因组学的单机构回顾性研究

A Prognostic and Carboplatin Response Predictive Model in Ovarian Cancer: A Mono-Institutional Retrospective Study Based on Clinics and Pharmacogenomics.

作者信息

Staropoli Nicoletta, Arbitrio Mariamena, Salvino Angela, Scionti Francesca, Ciliberto Domenico, Ingargiola Rossana, Labanca Caterina, Agapito Giuseppe, Iuliano Eleonora, Barbieri Vito, Cucè Maria, Zuccalà Valeria, Cannataro Mario, Tassone Pierfrancesco, Tagliaferri Pierosandro

机构信息

Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy.

Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 88100 Catanzaro, Italy.

出版信息

Biomedicines. 2022 May 23;10(5):1210. doi: 10.3390/biomedicines10051210.

Abstract

Carboplatin is the cornerstone of ovarian cancer (OC) treatment, while platinum-response, dependent on interindividual variability, is the major prognostic factor for long-term outcomes. This retrospective study was focused on explorative search of genetic polymorphisms in the Absorption, Distribution, Metabolism, Excretion (ADME) genes for the identification of biomarkers prognostic/predictive of platinum-response in OC patients. Ninety-two advanced OC patients treated with carboplatin-based therapy were enrolled at our institution. Of these, we showed that 72% of patients were platinum-sensitive, with a significant benefit in terms of OS ( = 0.001). We identified an inflammatory-score with a longer OS in patients with lower scores as compared to patients with the maximum score ( = 0.001). Thirty-two patients were genotyped for 1931 single nucleotide polymorphisms (SNPs) and five copy number variations (CNVs) by the DMET Plus array platform. Among prognostic polymorphisms, we found a potential role of UGT2A1 both as a predictor of platinum-response ( = 0.01) and as prognostic of survival ( = 0.05). Finally, we identified 24 SNPs related to OS. UGT2A1 correlates to an "inflammatory-score" and retains a potential prognostic role in advanced OC. These data provide a proof of concept that warrants further validation in follow-up studies for the definition of novel biomarkers in this aggressive disease.

摘要

卡铂是卵巢癌(OC)治疗的基石,而依赖个体差异的铂反应是长期预后的主要预测因素。这项回顾性研究聚焦于探索吸收、分布、代谢、排泄(ADME)基因中的基因多态性,以识别OC患者铂反应的预后/预测生物标志物。在我们机构招募了92例接受卡铂基治疗的晚期OC患者。其中,我们发现72%的患者对铂敏感,在总生存期方面有显著益处(P = 0.001)。我们确定了一种炎症评分,评分较低的患者与评分最高的患者相比,总生存期更长(P = 0.001)。通过DMET Plus阵列平台对32例患者进行了1931个单核苷酸多态性(SNP)和5个拷贝数变异(CNV)的基因分型。在预后多态性方面,我们发现UGT2A1既作为铂反应的预测指标(P = 0.01),又作为生存的预后指标(P = 0.05)具有潜在作用。最后,我们确定了24个与总生存期相关的SNP。UGT2A1与“炎症评分”相关,在晚期OC中保留潜在的预后作用。这些数据提供了一个概念验证,值得在后续研究中进一步验证,以确定这种侵袭性疾病的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fdc/9138265/f16ec4e4663d/biomedicines-10-01210-g001.jpg

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