中国胰腺腺癌患者KRAS野生型肿瘤的基因组突变和临床病理特征

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2025-04-22 DOI:10.1016/j.ygeno.2025.111048

Longyun Ye , Qinglin Fei , Tianjiao Li , Chang Lin , Huiyi Ou , Yiting Zhang , Yi Zhou , Jie Zhang , Kaizhou Jin , Xianjun Yu , Weiding Wu

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引用次数: 0

摘要

本研究旨在阐明中国KRAS野生型（WT）肿瘤患者胰腺导管腺癌（PDAC）的基因组和临床病理特征。对869例PDAC患者的分析显示，164例肿瘤（19%）为KRAS WT， TP53突变占主导地位（32%），其次是AHNAK（12%）、CTNNB1（6%）和BRAF（5%）。这些肿瘤表现出更高的DNA损伤反应基因突变发生率，肿瘤抗原CA-199、CA-125和CEA水平较低，并且在突变-等位基因肿瘤异质性和肿瘤突变负担方面具有相似的趋势。相反，在这些病例中，微卫星不稳定性明显升高。KRAS WT肿瘤的生存结果优于KRAS突变肿瘤，中位总生存期为36.5个月，而KRAS突变肿瘤为23.0个月(P <；0.0001)。这些发现表明，KRAS WT PDAC在中国患者中呈现出独特的遗传谱，需要开发特定的治疗策略。

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Genomic mutation and Clinicopathological features of KRAS wild-type tumors in Chinese cohort with pancreatic adenocarcinoma

This study aims to elucidate the genomic and clinicopathological characteristics of pancreatic ductal adenocarcinoma (PDAC) in Chinese patients with KRAS wild-type (WT) tumors. Analysis of 869 PDAC patients revealed that 164 tumors (19 %) were KRAS WT, with a predominance of TP53 mutations (32 %), followed by AHNAK (12 %), CTNNB1 (6 %), and BRAF (5 %). These tumors exhibited a higher prevalence of DNA damage response gene mutations, lower levels of tumor antigens CA-199, CA-125, and CEA, and with a similar trend in mutant-allele tumor heterogeneity and tumor mutational burden. Conversely, microsatellite instability was markedly elevated in these cases. Survival outcomes were superior for KRAS WT tumors, with a median overall survival of 36.5 months compared to 23.0 months for KRAS mutated tumors (P < 0.0001). These findings suggest that KRAS WT PDAC in Chinese patients presents a distinct genetic profile necessitating the development of specific therapeutic strategies.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.