文章：

突变KRAS与GATA6基因对胰腺腺癌化疗患者生存期的分层影响：一项前瞻性队列研究

Mutant KRAS and GATA6 Stratify Survival in Patients Treated with Chemotherapy for Pancreatic Adenocarcinoma: A Prospective Cohort Study

原文发布日期：5 March 2025

DOI: 10.3390/cancers17050896

类型: Article

开放获取: 是

英文摘要：

Background: Several pancreatic adenocarcinoma (PA) biomarkers beyond the traditional carbohydrate antigen (CA)19-9 have been identified but are lacking large-scale prospective validation. This prospective cohort study evaluated the prognostic impact of potential PA biomarkers. Methods: We enrolled 238 of 288 patients with histologically proven PA. We assessed candidate biomarkers, including CA19-9, germlineBRCA1/2, andATMmutations, as well as mutantKRAScirculating tumor DNA (ctDNA) in blood samples. Additionally, we evaluated the expression of SLC29A1 (hENT1), DCK, CES2, and GATA6. We examined the association of candidate biomarkers with progression-free survival (PFS) and overall survival (OS). Results: We analyzed biomarker efficacy in 200 (median age 65 years; 55% male) of the enrolled patients who received chemotherapy. A high mutantKRASctDNA concentration (hazard ratio [HR]: 1.508 and 95% confidence interval [CI]: 1.052–2.161 for PFS; HR: 1.796 and 95% CI: 1.203–2.681 for OS) and high CA19-9 level (HR: 1.647 and 95% CI: 1.177–2.306 for PFS; HR: 1.803 and 95% CI: 1.248–2.605 for OS) were associated with poor prognosis. High GATA6 RNA expression was linked to longer PFS (HR: 0.336 and 95% CI: 0.195–0.582) and OS (HR: 0.304 and 95% CI: 0.165–0.560). Conclusions: Plasma mutantKRASctDNA concentrations and GATA6 expression could serve as significant prognostic biomarkers in patients with PA, potentially guiding therapeutic decisions and prognostication.

摘要翻译： 

背景：除传统的糖类抗原（CA）19-9外，已发现多种胰腺腺癌（PA）生物标志物，但尚缺乏大规模前瞻性验证。本前瞻性队列研究评估了潜在PA生物标志物的预后影响。方法：在288例经组织学确诊的PA患者中，我们纳入了238例。我们评估了候选生物标志物，包括CA19-9、胚系BRCA1/2与ATM基因突变，以及血液样本中的KRAS突变循环肿瘤DNA（ctDNA）。此外，我们还评估了SLC29A1（hENT1）、DCK、CES2和GATA6的表达水平。我们分析了候选生物标志物与无进展生存期（PFS）和总生存期（OS）的关联。结果：在接受化疗的200例入组患者（中位年龄65岁；55%为男性）中进行了生物标志物效能分析。高KRAS突变ctDNA浓度（PFS风险比[HR]：1.508，95%置信区间[CI]：1.052–2.161；OS HR：1.796，95% CI：1.203–2.681）和高CA19-9水平（PFS HR：1.647，95% CI：1.177–2.306；OS HR：1.803，95% CI：1.248–2.605）与不良预后相关。高GATA6 RNA表达则与更长的PFS（HR：0.336，95% CI：0.195–0.582）和OS（HR：0.304，95% CI：0.165–0.560）相关。结论：血浆KRAS突变ctDNA浓度和GATA6表达可作为PA患者重要的预后生物标志物，可能为治疗决策和预后评估提供指导。

原文链接：

Mutant KRAS and GATA6 Stratify Survival in Patients Treated with Chemotherapy for Pancreatic Adenocarcinoma: A Prospective Cohort Study