Emerging histopathological prognostic biomarkers in hepatocellular carcinomas

PurposeHepatocellular carcinoma (HCC) is one of the most common malignant neoplasms and is associated with a poor survival rate. An increased understanding of the molecular mechanisms underlying HCC carcinogenesis and progression has enabled the identification of many potential HCC biomarkers. In addition to predicting prognosis and recurrence, these markers may guide decisions regarding therapeutic intervention of potential targets and appropriate therapeutic modalities for individual patients. Considering the high recurrence rate associated with HCC resection, improved biomarkers that can be used for early diagnosis, predicting recurrence, and monitoring progression are urgently needed in clinical practice.Study section and resultsThis systematic review examines evidence from published studies that have reported emerging prognostic biomarkers, paying particular attention to markers evaluated by histopathological analysis of resected HCC tissues. These markers include molecules involved in cellular proliferation and survival (e.g. cyclins and cyclin dependent kinase inhibitors, mutant p53, and hepatocyte growth factor receptor [c-MET]), aberrantly expressed cell surface proteins (e.g. glypican 3, monocarboxylate transporter 4, and hepatocyte growth factor activator inhibitor type 1), and factors found in altered tumor microenvironments (e.g. angiogenesis factors, regulatory T-cells, tumor-associated macrophages, and hepatic stellate cells).ConclusionIdentification of novel, effective biomarkers for the diagnosis and prognosis of HCC is critical for the improvement of companion diagnostics in personalized oncology therapies for HCC. The molecules described in this review are attractive candidates for future HCC biomarkers to be used in clinical oncology practice.