Nusrat Faria, Gorgov Eliyahu, Khanna Akshay, Isesele Obehioye, Bowne Wilbur, Lavu Harish, Yeo Charles J, Jiang Wei, Jain Aditi, Nevler Avinoam
Sidney Kimmel Cancer Center, Department of Pathology, Thomas Jefferson University, Philadelphia, PA.
Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA.
Pancreas. 2025 May 1;54(5):e449-e454. doi: 10.1097/MPA.0000000000002458.
Pancreatic ductal adenocarcinoma (PDAC) has a distinct genomic profile, with somatic KRAS mutations occurring in 85%-95% of all PDAC cases. This study aimed to measure the prognostic impact of specific KRAS mutations in resected PDAC patients from a large, high-volume center.
This retrospective study included a cohort of PDAC patients who underwent curative-intent pancreatic resection at our institution between 2016 and 2021. Demographic, histologic, and oncologic outcome data were recorded. KRAS status was assessed via next-generation sequencing. Thirty-six (12.8%) wtKRAS, 109 (38.8%) G12D, 76 (27.0%) G12V, 36 (12.8%) G12R, 11 (3.9%) Q61H.
A total of 281 patients were included with wtKRAS (12.8%), G12D (38.8%), G12V (27.0%), G12R (12.8%), accounting for over 90% of the KRAS genotypes. Kaplan-Meier analysis revealed wild-type KRAS to be associated with improved overall survival (68.5±0 vs. 32.1±2.3 mo, P=0.005), and disease-free survival (35.4±0 vs. 20.3±3.9 mo, P=0.043). Cox regression analysis demonstrated worse overall survival with increased age (HR=1.04/y, P<0.01), neoadjuvant chemotherapy (HR=2.01, P<0.01), the presence of lymphovascular invasion (HR=2.47, P<0.01), G12D or G12V KRAS subtypes (P≤0.05), and lack of adjuvant chemotherapy (HR=0.6, P=0.02).
Next-generation sequencing of the KRAS subtype in resectable PDAC tumors shows that the KRAS G12D/G12V subtypes confer a worse prognosis compared with wild-type KRAS tumors.
胰腺导管腺癌（PDAC）具有独特的基因组特征，85%-95%的PDAC病例存在KRAS体细胞突变。本研究旨在评估来自大型高容量中心的接受手术切除的PDAC患者中特定KRAS突变的预后影响。
这项回顾性研究纳入了2016年至2021年间在本机构接受根治性胰腺切除术的PDAC患者队列。记录人口统计学、组织学和肿瘤学结局数据。通过二代测序评估KRAS状态。36例（12.8%）野生型KRAS，109例（38.8%）G12D，76例（27.0%）G12V，36例（12.8%）G12R，11例（3.9%）Q61H。
共纳入281例患者，野生型KRAS（12.8%）、G12D（38.8%）、G12V（27.0%）、G12R（12.8%），占KRAS基因型的90%以上。Kaplan-Meier分析显示野生型KRAS与总生存期改善相关（68.5±0对32.1±2.3个月，P=0.005），以及无病生存期改善相关（35.4±0对20.3±3.9个月，P=0.043）。Cox回归分析显示，年龄增加（HR=1.04/年，P<0.01）、新辅助化疗（HR=2.01，P<0.01）、存在脉管侵犯（HR=2.47，P<0.01）、G12D或G12V KRAS亚型（P≤0.05）以及未进行辅助化疗（HR=0.6，P=0.02）与总生存期较差相关。
可切除的PDAC肿瘤KRAS亚型的二代测序显示，与野生型KRAS肿瘤相比，KRAS G12D/G12V亚型的预后更差。
