The Circulating Cholangiocarcinoma Protein Biomarkers CRP and MASP2 Also Predict Gallbladder Cancer Risk

Area of Science:

• Oncology
• Biomarker Discovery
• Proteomics

Background:

• Primary sclerosing cholangitis (PSC) patients with cholangiocarcinoma (CCA) show predictive serum biomarker differences.
• Previous research identified serum biomarkers predicting CCA development before clinical symptoms.

Purpose of the Study:

• To investigate if previously identified CCA biomarkers (CRP and MASP2) predict gallbladder cancer (GBC) risk.
• To develop a predictive model for GBC risk using serum protein levels and clinical data.

Main Methods:

• Analysis of European prospective plasma samples from 24 GBC cases and 90 controls.
• Protein quantification using timsTOF PRO mass spectrometry, followed by logarithmic transformation and quantile normalization.
• Univariate logistic regression and backward model selection for risk prediction model development.

Main Results:

• Serum levels of C-reactive protein (CRP) and MASP2 were found to be predictive of GBC risk (p < 0.05).
• A combined model of CRP, MASP2, and age at blood sampling achieved an area under the curve (AUC) of 0.80 for GBC risk prediction.
• CRP mRNA levels were elevated in Chilean GBC cases, while MASP2 mRNA showed an opposing trend.

Conclusions:

• Circulating CRP and MASP2 levels are associated with the risk of both CCA and GBC in European populations.
• These findings suggest potential shared mechanisms in the development of CCA and GBC.
• Further research is warranted to explore prevention strategies for these aggressive biliary tract cancers.