A bile acid-related prognostic signature in hepatocellular carcinoma

Abstract

Due to the high mortality of hepatocellular carcinoma (HCC), its prognostic models are urgently needed. Bile acid (BA) metabolic disturbance participates in hepatocarcinogenesis. We aim to develop a BA-related gene signature for HCC patients. Research data of HCC were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) online databases. After least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a BA-related prognostic signature in TCGA cohort based on differentially expressed prognostic BA-related genes. Then, the predictive performance of the signature was evaluated and verified in TCGA and ICGC cohort respectively. We obtained the risk score of each HCC patient according to the model. The differences of immune status and drug sensitivity were compared in patients that were stratified based on risk score. The protein and mRNA levels of the modeling genes were validated in the Human Protein Atlas database and our cell lines, respectively. In TCGA cohort, we selected 4 BA-related genes to construct the first BA-related prognostic signature. The risk signature exhibited good discrimination and predictive ability, which was verified in ICGC cohort. Patients were classified into high- and low-risk groups according to their median scores. The occurrence of death increased with increasing risk score. Low-risk patients owned favorable overall survival. High-risk patients possessed high immune checkpoint expression and low IC50 values for sorafenib, cisplatin and doxorubicin. Real-time quantitative PCR and immunohistochemical results validate expression of modeling genes in the signature. We constructed the first BA-related gene signature, which might help to identify HCC patients with poor prognosis and guide individualized treatment.

Multi-omics integrated analyzed the origin of intrahepatic mucinous cholangiocarcinoma: a case report

“…This may be one of the mechanisms by which IMCC occurs. Previous studies also support our speculation (12,13). A Gene Set Enrichment Analysis (GSEA) was also performed, which showed that oxygen-linked mucin glycosylation was activated in IMCC (Figure 1C).…”

Sex Dimorphic Effects of Bile Acid Metabolism in Liver Cancer in Mice

“… 50 Moreover, several reported molecular signatures and computational models based on bile acid metabolism-related genes were found to effectively predict the prognosis of HCC patients and their immunotherapeutic response. 50 , 51 , 52 , 53 , 54 A few available reports hint the possibility that bile acid metabolism could explain sex divergences in liver disease pathologies. One 2007 study highlights a female-specific resistance in hepatotoxic and cholestasis mouse models due to their better bile acid detoxification.…”