KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

• Published in: Journal of hematology and oncology Vol. 18; no. 1; pp. 44 - 4
• Main Authors: Yousef, Mahmoud, Yousef, Abdelrahman, Hurd, Mark W., Pillai, Ashwathy, Chowdhury, Saikat, Snyder, Rebecca, Knafl, Mark, Lewis, Ryan L., Roy, Paul M., Fanaeian, Mohammad, Albarouki, Sali, Castelnovo, Luca F., Peterson, Jennifer, Smaglo, Brandon G., Wolff, Robert A., Pant, Shubham, Willis, Jason, Huey, Ryan, Overman, Michael, Tzeng, Ching-Wei, Kim, Michael P., Ikoma, Naruhiko, Maxwell, Jess E., Katz, Matthew H. G., Wang, Huamin, Maitra, Anirban, Koay, Eugene, Ludmir, Ethan B., Chen, Anthony, Lopez, Camila, Ying, Haoqiang, Shen, John Paul, Zhao, Dan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.04.2025; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Pancreatic Ductal - diagnosis; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Correspondence; Female; Genomes; Humans; KRAS; Liquid biopsy; Liquid Biopsy - methods; Male; Metastases; Metastasis; Middle Aged; Molecular profiling; Mutation; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patients; PDAC; Proto-Oncogene Proteins p21(ras) - genetics; Tumor proteins; PDAC; OS; Pancreatic cancer; Liquid biopsy; KRAS; Molecular profiling; Mutation
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-025-01696-0

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity ( N = 186) in metastatic cases and in 52.4% ( N = 43) of localized disease. KRAS mutations were detected in 64.6% ( N = 148) of metastatic cases and 16% ( N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7–4.3, P < 0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% ( KRAS ) and 33% ( TP53 ) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.