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

In a recent publication, Lapitz et al. reported differences in serum levels that predict the development of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis prior to clinical manifestation. We examined whether these biomarkers also predict the risk of gallbladder cancer (GBC) in European prospective plasma samples from 24 GBC cases and 90 control individuals. After logarithmic transformation and quantile normalisation of individual protein levels measured with a timsTOF PRO mass spectrometer, we fitted univariate logistic regression models and applied backward model selection to identify the optimal model for GBC risk prediction. CRP and MASP2, previously reported markers of CCA, were found to be predictive for GBC risk as well (p value < 0.05), and complemented by age at blood sampling, provided an area under the receiver operating characteristic curve of 0.80 (95% confidence interval 0.69-0.92) when combined in a prediction model for GBC risk. We further examined the mRNA expression of CRP and MASP2 in serum samples from 82 GBC cases and 79 control subjects from Chile. CRP mRNA levels were elevated in Chilean GBC cases, but MASP2 showed an opposite trend. While there are considerable differences in the design of the discovery study and ours, the finding that circulating levels of CRP and MASP2 are associated with the risk of both CCA and GBC in Europeans highlights the need for further research into potential shared mechanisms and strategies for the prevention of these two aggressive biliary tumours.