Proteomic analysis and translational perspective of hepatocellular carcinoma: Identification of diagnostic protein biomarkers by an onco-proteogenomics approach

Hepatocellular carcinoma (HCC) has been ranked as the third leading cause of cancer-related mortality worldwide. Typically, patients are already in advanced stages of liver cirrhosis at the time of HCC diagnosis. Because HCC is often detected at a late stage and is highly aggressive, noninvasive biomarkers are urgently needed for early diagnosis. Recent advances in gene-expression profiling technologies have enabled molecular classification of HCC into defined subclasses that provide a firm basis for further study of potential mechanisms and biomarkers underlying the development of HCC. This study applied an integrated onco-proteogenomics approach to identify and characterize HCC biomarkers. Specifically, this study integrated proteomic, genomic, and transcriptomic methods to obtain protein expression profiles of urine and tissue samples from HCC patients and from normal controls. Two mediators of inflammation were positively identified: S100A9 and granulin protein markers, which belong to the cytoplasmic alarmin family of the host innate immune system. These HCC-associated cancer-specific biomarkers may have contributing roles not only in the dysregulated processes associated with various inflammatory and autoimmune conditions, but also in tumorigenesis and cancer metastasis.