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高级别浆液性卵巢癌中临床和肿瘤突变特征的预后相关性

Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer.

作者信息

Martín-Vallejo Javier, Berenguer-Marí Juan Ramón, Bosch-Romeu Raquel, Sierra-Roca Julia, Tadeo-Cervera Irene, Pardo Juan, Falcó Antonio, Molina-Bellido Patricia, Laforga Juan Bautista, Clemente-Pérez Pedro Antonio, Gasent-Blesa Juan Manuel, Climent Joan

机构信息

Department of Obstetrics and Gynecology, Hospital de Denia, 03700 Alicante, Spain.

Department of Medical Oncology, Hospital de Denia, 03700 Alicante, Spain.

出版信息

Int J Mol Sci. 2025 Aug 1;26(15):7416. doi: 10.3390/ijms26157416.

Abstract

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations ( = 0.0035), as well as mutations in ( = 0.044), ( = 0.023), ( = 0.03), and ( = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology.

摘要

高级别浆液性卵巢癌(HGSOC)是卵巢癌最常见且侵袭性最强的亚型,约占病例的70%。本研究调查了接受初次肿瘤细胞减灭术加辅助化疗(PDS)或新辅助化疗加间隔肿瘤细胞减灭术(NACT)的患者的基因突变及其与总生存期(OS)、完全肿瘤细胞减灭(R0)和铂类反应的关联。通过下一代测序(NGS)对43例原发性HGSOC肿瘤样本进行靶向大规模平行测序,进行基因分析。对临床和分子数据进行综合评估,并通过PDS和NACT队列之间的亚组比较进行评估。所有分析样本均存在基因改变。单因素生存分析显示,突变总数( = 0.0035)以及 ( = 0.044)、 ( = 0.023)、 ( = 0.03)和 ( = 0.007)中的突变与较差的OS显著相关。整合临床和分子数据的多因素Cox回归证实, 突变与不良预后独立相关。这些发现揭示了PDS组和NACT组之间独特的突变图谱,并表明 改变可能定义了一种特别侵袭性的肿瘤表型。本研究有助于更深入地了解HGSOC生物学,并可能支持在精准肿瘤学背景下开发新的治疗靶点和个性化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545e/12347516/cca22d3e8276/ijms-26-07416-g001.jpg

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