Abstract
BACKGROUND & AIMS: Currently, preoperative diagnostic methods that can distinguish cancer from benign disease of the gallbladder are insufficient, and several surgical resections can be avoided if the pathology is known prior to surgery. This study aimed to assess whether preoperative plasma proteins can distinguish gallbladder cancer (GBC) from cholecystitis, with the main goal of identifying proteins for multivariate description of the postoperative diagnosis, before surgery. METHODS: Samples from 82 individuals with suspected GBC who underwent bisegmentectomy and lymphadenectomy at Karolinska University Hospital between 2009 and 2020 were included in this retrospective, observational, single-center study. Preoperative plasma samples were analyzed using a 7,500 proteomics panel from SomaScan®. High-dimensional statistical methods including machine learning regularization, were used to analyze the data. RESULTS: In our study, we identified and characterized a panel of 651 proteins that exhibited differential expression between GBC and cholecystitis. Through multivariate analysis, we demonstrated that circulating proteomics data provide valuable insights for diagnosing GBC before surgical intervention. Notably, we identified a subset of eight plasma proteins (PAHX, CD8A, HRG, CRIS2, Dynactin subunit 2, AT2A3, CSTN2, and DEPP) that effectively differentiated GBC from cholecystitis with a diagnostic accuracy of 94% when validated on a test set. These findings hold potential for clinical validation and could significantly aid in preoperative decision-making when GBC is suspected. CONCLUSIONS: Our findings demonstrate that the preoperative assessment of plasma proteins can accurately differentiate cholecystitis from malignancy, supporting the potential development of a noninvasive test to assist preoperative decision-making when GBC is suspected. IMPACT AND IMPLICATIONS: This study highlights the potential of plasma proteomic profiling to significantly improve the preoperative diagnostic accuracy of gallbladder cancer vs. cholecystitis. Using machine learning models, we identified biologically relevant plasma proteins associated with the diagnosis of gall bladder cancer. A noninvasive preoperative test based on selected plasma proteins could potentially enhance clinical decision-making, reduce unnecessary surgeries, and mitigate the associated risks for patients with suspected GBC, marking a step forward in precision medicine.