Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
MassARRAY-based KRAS and GNAS hotspot mutation analysis of cystic fluid enables accurate classification of pancreatic cystic lesions
Wen-Fei Diao, Ming Cui, Tian-Qi Chen, Jin-Heng Xiao, Sen Yang, Qing-Yuan Zheng, Rui-Yuan Xu, Xian-Lin Han, Ya Hu
Wen-Fei Diao, Ming Cui, Jin-Heng Xiao, Sen Yang, Qing-Yuan Zheng, Rui-Yuan Xu, Xian-Lin Han, Ya Hu, Department of General Surgery, Peking Union Medical College Hospital, Beijing 100730, China
Wen-Fei Diao, Ming Cui, Jin-Heng Xiao, Sen Yang, Rui-Yuan Xu, Xian-Lin Han, Ya Hu, Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Wen-Fei Diao, Ming Cui, Jin-Heng Xiao, Sen Yang, Rui-Yuan Xu, Ya Hu, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Wen-Fei Diao, Ming Cui, Jin-Heng Xiao, Sen Yang, Rui-Yuan Xu, Ya Hu, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Tian-Qi Chen, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Co-first authors: Wen-Fei Diao and Ming Cui.
Co-corresponding authors: Xian-Lin Han and Ya Hu.
Author contributions: Diao WF, Cui M and Chen TQ conceptualized and designed the study; Diao WF, Chen TQ, Xiao JH and Yang S collected the data and cystic fluids sample; Xu RY is responsible for data curation; Diao WF, Cui M and Zheng QY performed data analysis; Diao WF and Cui M prepared the manuscript; Hu Y and Han XL supervised the study and performed draft reviewing and editing. Since Diao WF and Cui M contributed equally for the study completion and manuscript writing, they were listed as co-first authors. Hu Y and Han XL were listed as co-correspondence as they contributed equally in study supervision and draft reviewing. All authors contributed to this study and approved the manuscript to be published.
Supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project, No. 2025ZD0552402; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, No. 2023-I2M-2-002; National High-Level Hospital Clinical Research Funding, No. 2022-PUMCH-D-001; Peking Union Medical College Hospital Talent Cultivation Program, Category D, No. UHB12625; and Milstein Medical Asian American Partnership (MMAAP) Foundation.
Institutional review board statement: The study was approved by the Ethics Committee of Peking Union Medical College Hospital (No. I-23PJ1601), in accordance with the ethical standards of the Institutional Research Committee and with the Helsinki declaration.
Informed consent statement: Informed consents were obtained from all participants in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author Ya Hu, upon reasonable request at
huya@pumch.cn.
Corresponding author: Ya Hu, MD, Professor, Department of General Surgery, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.
huya@pumch.cn
Received: October 24, 2025
Revised: December 1, 2025
Accepted: February 3, 2026
Published online: April 7, 2026
Processing time: 154 Days and 20.1 Hours
BACKGROUND
Pancreatic cystic fluid analysis through mutation sequencing has proven to be a valuable approach for classifying pancreatic cystic lesions (PCLs). However, a rapid and cost-effective method for screening these lesions is still needed.
AIM
To evaluate the application of MassARRAY system in detecting hotspot mutation for the rapid diagnosis of PCLs.
METHODS
A total of 101 surgically resected PCLs were analyzed in this study. DNA was extracted from intraoperatively collected pancreatic cystic fluid. A custom panel targeting KRAS and GNAS hotspot mutations was developed, and the performance of MassARRAY-based mutation detection in classifying PCLs was evaluated.
RESULTS
Intraductal papillary mucinous neoplasms (IPMNs) exhibited GNAS mutations in 52.2% and KRAS mutations in 39.1% of cases, with 33.3% showing both mutations. KRAS mutations were detected in 30.6% of mucinous cystic neoplasms (MCNs), while serous cystadenomas and non-neoplastic neoplasms showed no detectable mutations. A logistic regression model integrating KRAS and GNAS mutations in pancreatic cystic fluid, along with serum tumor biomarkers and clinical features, achieved an area under the curve greater than 0.9 for identification of IPMNs and 0.795 for MCNs.
CONCLUSION
Targeted hotspot mutation analysis of KRAS and GNAS with MassARRAY technique in pancreatic cystic fluid offers a promising application for the molecular classification of PCLs. This method holds significant potential for improving preoperative diagnosis and assisting clinical decision-making in the management of PCLs.
Core Tip: Pancreatic cystic lesions (PCLs) are highly heterogenous, which included benign, pre-malignant and malignant lesions. Current diagnostic approaches for PCLs exhibit limited efficacy and accuracy. The implementation of MassARRAY-based KRAS and GNAS mutation analysis of pancreatic cystic fluids improves the precise identification of mucinous cysts and intraductal papillary mucinous neoplasms, thereby providing critical support for clinical decision-making.
