Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome
Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome
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DOI：
10.1245/s10434-021-11081-z
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发表时间：
2021-11-18
影响因子：
3.7
通讯作者：
Yu, Jun
中科院分区：
文献类型：
--
作者：
Shoucair, Sami;Habib, Joseph R.;Yu, Jun
背景资料。胰腺导管腺癌(PDAC)的预后仍然很差，尽管系统治疗和外科技术有所改进。识别生物标记物以促进对肿瘤生物学的洞察并实现更好的个体化预后可能有助于改善预后。我们的目的是阐明四个主要驱动基因突变(KRAS、TP53、Smad4、CDKN2A)及其组合在切除的PDAC.Patient和方法中的预后作用。使用cBioPortalTM数据库和美国国家癌症研究所的癌症基因组图谱(TCGA)对2012-2020年间接受早期切除的PDAC进行下一代测序的患者进行回顾性分析。采用多变量Cox回归分析风险调整后的总体(OS)和无复发生存率(RFS)预测因素。结果：在发现的队列中(n=587)，突变的驱动基因的数量增加与较差的OS相关(p=0.047)。具体地说，具有>；=2的驱动基因突变的患者的OS比
Background. Prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (KRAS, TP53, SMAD4, CDKN2A) and their combinations in resected PDAC.Patients and Methods. A retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute's Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.'Results. In the discovery cohort (n = 587), increased number of mutated driver genes was associated with worse OS (p = 0.047). Specifically, patients with mutations in >= 2 driver genes had worse OS than