Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028,p= 0.029; HR 2.081, 95% CI 1.014–4.272,p= 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049,p= 0.045; HR 2.229, 95% CI 1.082–4.594,p= 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detectingKRASmutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.
背景/目的：胰腺导管腺癌（PDAC）发病率持续上升，由于诊断延迟及有效治疗手段有限，其预后仍然较差。目前患者治疗主要依据TNM分期，缺乏肿瘤分子特征分析。本研究旨在验证一种结合扩增阻滞突变系统（ARMS）与高分辨率熔解曲线分析（HRMA）的技术，用于检测肿瘤组织和血浆中KRAS基因12号密码子突变，并评估其预后价值。方法：前瞻性研究纳入初诊PDAC患者，采集治疗前肿瘤组织及血浆样本。采用ARMS-HRMA技术检测KRAS 12号密码子突变（G12D、G12V、G12C、G12R），并与Sanger测序（SS）进行对比。通过单因素及多因素分析评估这些突变的预后意义。结果：共纳入88例患者，93% ECOG-PS评分0-1分，57%为可切除病例。ARMS-HRMA技术在肿瘤组织（77% vs. 51%）和血浆（25% vs. 0%）中均显示出比SS更高的检测灵敏度。最常见突变类型为G12D（32例，36%），其次为G12V（22例，25%）。多因素分析显示，肿瘤组织或血浆中存在G12D和/或G12C突变的患者，其无进展生存期（HR 1.792，95% CI 1.061–3.028，p=0.029；HR 2.081，95% CI 1.014–4.272，p=0.046）和总生存期（HR 1.757，95% CI 1.013–3.049，p=0.045；HR 2.229，95% CI 1.082–4.594，p=0.030）均显著缩短。结论：ARMS-HRMA是一种快速、经济的PDAC患者KRAS突变检测方法，具有预后分层和指导治疗决策的潜力。肿瘤组织与血浆中G12D和G12C突变的存在与不良预后相关。
肿瘤(癌症)患者之家