Proteome Landscape of Early Stage Hepatocellular Carcinoma Identifies Proteomic Subtypes and New Therapeutic Targets - Phosphorylation data

ABSTRACT: Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.

OTHER RELATED OMICS DATASETS IN: GSE124535

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: yang zhao  

LAB HEAD: Fuchu He

PROVIDER: PXD008373 | Pride | 2019-03-01

REPOSITORIES: pride