Novel serum biomarkers in intrahepatic cholangio-carcinoma: a pilot proteomic exploration

Cholangiocarcinoma (CCA) is a highly aggressive form of biliary tract cancer arising from the malignant transformation of cholangiocytes. A fundamental hurdle lies in comprehending the underlying biology of CCA tumorigenesis, as it holds significance for early detection and intervention. Monitoring alterations in protein abundance within serological proteomes throughout the course of disease progression can offer invaluable insights into the intricacies of CCA physiology and pathology. This study aimed to explore the serum proteome of patients with intrahepatic CCA (iCCA), hepatocellular carcinoma (HCC), liver cirrhosis (CIR), primary sclerosing cholangitis (PSC), to identify new biomarker candidates along with possible pathways involved in the development of these complications. By using high-throughput mass spectrometry proteomics analysis, significant differences were identified. Notably, serum amyloid A1 and A4 (SAA1, SAA4), along with Vascular cell adhesion molecule 1 (VCAM-1) and angiopoietin-1 receptor (TEK), were found to have discriminatory power between iCCA and HCC. Heat shock protein 90 (HSP90), Annexin A9 (ANXA9), alpha-1-antichymotrypsin (SERPINA3) and Leucine-rich alpha-2-glycoprotein (LRG1) were highlighted for evidencing risk factors, such as CIR and PSC. This first pilot proteomic analysis underscores the reliability of identifying promising novel biomarker candidates for iCCA. Further validation and exploration of these serum proteins' clinical utility are warranted.