2025-03-03 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/new-biomarkers-may-improve-diagnosis-of-gallbladder-cancer
- https://www.jhep-reports.eu/article/S2589-5559(25)00042-4/fulltext
胆嚢がん疑いの血漿プロテオミクスプロファイリングによる精密医療戦略に向けて:パイロットスタディ Towards precision medicine strategies using plasma proteomic profiling for suspected gallbladder cancer: a pilot study
Ghada Nouairia, PhD∙ Martin Cornillet, PhD∙ Hannes Jansson, MD PhD∙ Annika Bergquist, MD PhD∙ Ernesto Sparrelid, MD PhD
JHEP Reports Published:February 21, 2025
DOI:https://doi.org/10.1016/j.jhepr.2025.101365
Graphical abstract
Highlights:
•The plasma proteome can differentiate gallbladder cancer from cholecystitis with high accuracy.
•Machine learning models can identify a biologically relevant subset of differentiating plasma proteins.
•Plasma protein tests could have the potential to assist in preoperative decision-making when GBC is suspected.
Abstract
Background and 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, prior to 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 (ML) regularization, were employed to analyze the data.
Results
In our study, we identified and characterized a panel of 651 proteins that exhibited differential expression between gallbladder cancer (GBC) and cholecystitis. Through multivariate analysis, we demonstrated that circulating proteomics data provide valuable insights for diagnosing GBC prior to surgical intervention. Notably, we identified a subset of 8 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 versus cholecystitis. Using ML models, we identified biologically relevant plasma proteins associated with the diagnosis of GBC. 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.
