Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma
L. Whitney, Limin Wang, Marshonna Forgues, Jinping Liu, Siritida Rabibhadana, Benjarath Pupacdi, Yongmei Zhao, Heelah Gholian, Vajarabhongsa Bhudhisawasdi, Chawalit Pairojkul, Wattana Sukeepaisarnjaroen, Ake Pugkhem, Vor Luvira, Nirush Lertprasertsuke, Anon Chotirosniramit, Chirayu Auewarakul, Teerapat Ungtrakul, Thaniya Sricharunrat, Suleeporn Sangrajrang, Kannika Phornphutkul, Anuradha Budhu, Curtis C. Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin Wei Wang
Abstract
This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.