Machine Learning‐Based Radiomics in Malignancy Prediction of Pancreatic Cystic Lesions: Evidence from Cyst Fluid Multi‐Omics

Abstract The malignant potential of pancreatic cystic lesions (PCLs) varies dramatically, leading to difficulties when making clinical decisions. This study aimed to develop noninvasive clinical‐radiomic models using preoperative CT images to predict the malignant potential of PCLs. It also investigates the biological mechanisms underlying these models. Patients from two retrospective and one prospective cohort, all undergoing surgical resection for PCLs, are divided into four datasets: training, internal test, external test, and prospective application sets. Eleven machine learning classifiers are employed to construct radiomic models based on selected features. Cyst fluid from the prospective cohort is collected for proteomic and lipidomic analysis. The radiomic models demonstrated high accuracy, with area under the receiver operating characteristic curves (AUCs) > 0.93 across the training (n = 262), internal test (n = 50), and external test (n = 50) sets. AUCs ranged from 0.92 to 0.96 for the prospective cohort (n = 34). Meanwhile, differentially‐expressed proteins and lipid molecules, along with their associated signaling pathways, are identified between high and low groups of clinical‐radiomic scores. This models can effectively and accurately predict the malignant potential of PCLs, with multi‐omics evidence suggesting the biological mechanisms involving secretion function and lipid metabolism underlying clinical‐radiomic models.