KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

Mahmoud Yousef; Abdelrahman Yousef; Mark W. Hurd; Ashwathy Pillai; Saikat Chowdhury; Rebecca Snyder; Mark Knafl; Ryan L. Lewis; Paul M. Roy; Mohammad Fanaeian; Sali Albarouki; Luca F. Castelnovo; Jennifer Peterson; Brandon G. Smaglo; Robert A. Wolff; Shubham Pant; Jason Willis; Ryan Huey; Michael Overman; Ching Wei Tzeng; Michael P. Kim; Naruhiko Ikoma; Jess E. Maxwell; Matthew H.G. Katz; Huamin Wang; Anirban Maitra; Eugene Koay; Ethan B. Ludmir; Anthony Chen; Camila Lopez; Haoqiang Ying; John Paul Shen; Dan Zhao

doi:10.1186/s13045-025-01696-0

KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

Mahmoud Yousef, Abdelrahman Yousef, Mark W. Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L. Lewis, Paul M. Roy, Mohammad Fanaeian, Sali Albarouki, Luca F. Castelnovo, Jennifer Peterson, Brandon G. Smaglo, Robert A. Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching Wei TzengMichael P. Kim, Naruhiko Ikoma, Jess E. Maxwell, Matthew H.G. Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B. Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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.

Original language	English (US)
Article number	44
Pages (from-to)	44
Journal	Journal of Hematology and Oncology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s13045-025-01696-0
State	Published - Dec 2025

Keywords

KRAS
Liquid biopsy
Molecular profiling
Mutation
OS
PDAC
Pancreatic cancer
Humans
Proto-Oncogene Proteins p21(ras)/genetics
Middle Aged
Pancreatic Neoplasms/genetics
Male
Liquid Biopsy/methods
Aged, 80 and over
Female
Adult
Aged
Carcinoma, Pancreatic Ductal/genetics

ASJC Scopus subject areas

Hematology
Molecular Biology
Oncology
Cancer Research

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10.1186/s13045-025-01696-0

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Yousef, M., Yousef, A., Hurd, M. W., Pillai, A., Chowdhury, S., Snyder, R., Knafl, M., Lewis, R. L., Roy, P. M., Fanaeian, M., Albarouki, S., Castelnovo, L. F., Peterson, J., Smaglo, B. G., Wolff, R. A., Pant, S., Willis, J., Huey, R., Overman, M., ... Zhao, D. (2025). KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma. Journal of Hematology and Oncology, 18(1), 44. Article 44. https://doi.org/10.1186/s13045-025-01696-0

Yousef, M, Yousef, A, Hurd, MW, Pillai, A, Chowdhury, S, Snyder, R, Knafl, M, Lewis, RL, Roy, PM, Fanaeian, M, Albarouki, S, Castelnovo, LF, Peterson, J, Smaglo, BG, Wolff, RA, Pant, S, Willis, J, Huey, R, Overman, M, Tzeng, CW, Kim, MP, Ikoma, N, Maxwell, JE, Katz, MHG, Wang, H, Maitra, A, Koay, E, Ludmir, EB, Chen, A, Lopez, C, Ying, H, Shen, JP & Zhao, D 2025, 'KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma', Journal of Hematology and Oncology, vol. 18, no. 1, 44, pp. 44. https://doi.org/10.1186/s13045-025-01696-0

@article{c13d2abd4fe043feaa7084e0318b8217,

title = "KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma",

abstract = "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.",

keywords = "KRAS, Liquid biopsy, Molecular profiling, Mutation, OS, PDAC, Pancreatic cancer, Humans, Proto-Oncogene Proteins p21(ras)/genetics, Middle Aged, Pancreatic Neoplasms/genetics, Male, Liquid Biopsy/methods, Aged, 80 and over, Female, Adult, Aged, Carcinoma, Pancreatic Ductal/genetics",

author = "Mahmoud Yousef and Abdelrahman Yousef and Hurd, \{Mark W.\} and Ashwathy Pillai and Saikat Chowdhury and Rebecca Snyder and Mark Knafl and Lewis, \{Ryan L.\} and Roy, \{Paul M.\} and Mohammad Fanaeian and Sali Albarouki and Castelnovo, \{Luca F.\} and Jennifer Peterson and Smaglo, \{Brandon G.\} and Wolff, \{Robert A.\} and Shubham Pant and Jason Willis and Ryan Huey and Michael Overman and Tzeng, \{Ching Wei\} and Kim, \{Michael P.\} and Naruhiko Ikoma and Maxwell, \{Jess E.\} and Katz, \{Matthew H.G.\} and Huamin Wang and Anirban Maitra and Eugene Koay and Ludmir, \{Ethan B.\} and Anthony Chen and Camila Lopez and Haoqiang Ying and Shen, \{John Paul\} and Dan Zhao",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = dec,

doi = "10.1186/s13045-025-01696-0",

language = "English (US)",

volume = "18",

pages = "44",

journal = "Journal of Hematology and Oncology",

issn = "1756-8722",

publisher = "BioMed Central Ltd.",

number = "1",

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TY - JOUR

T1 - KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

AU - Yousef, Mahmoud

AU - Yousef, Abdelrahman

AU - Hurd, Mark W.

AU - Pillai, Ashwathy

AU - Chowdhury, Saikat

AU - Snyder, Rebecca

AU - Knafl, Mark

AU - Lewis, Ryan L.

AU - Roy, Paul M.

AU - Fanaeian, Mohammad

AU - Albarouki, Sali

AU - Castelnovo, Luca F.

AU - Peterson, Jennifer

AU - Smaglo, Brandon G.

AU - Wolff, Robert A.

AU - Pant, Shubham

AU - Willis, Jason

AU - Huey, Ryan

AU - Overman, Michael

AU - Tzeng, Ching Wei

AU - Kim, Michael P.

AU - Ikoma, Naruhiko

AU - Maxwell, Jess E.

AU - Katz, Matthew H.G.

AU - Wang, Huamin

AU - Maitra, Anirban

AU - Koay, Eugene

AU - Ludmir, Ethan B.

AU - Chen, Anthony

AU - Lopez, Camila

AU - Ying, Haoqiang

AU - Shen, John Paul

AU - Zhao, Dan

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

KW - KRAS

KW - Liquid biopsy

KW - Molecular profiling

KW - Mutation

KW - OS

KW - PDAC

KW - Pancreatic cancer

KW - Humans

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Middle Aged

KW - Pancreatic Neoplasms/genetics

KW - Male

KW - Liquid Biopsy/methods

KW - Aged, 80 and over

KW - Female

KW - Adult

KW - Aged

KW - Carcinoma, Pancreatic Ductal/genetics

UR - https://www.scopus.com/pages/publications/105003198550

UR - https://www.scopus.com/inward/citedby.url?scp=105003198550&partnerID=8YFLogxK

U2 - 10.1186/s13045-025-01696-0

DO - 10.1186/s13045-025-01696-0

M3 - Article

C2 - 40247392

AN - SCOPUS:105003198550

SN - 1756-8722

VL - 18

SP - 44

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

IS - 1

M1 - 44

ER -

KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma

Abstract

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