Implication of TRPM8, CD47, and CDK4 expressions in hepatocellular carcinoma progression

Participation of TRPM8 in hepatocellular carcinoma (HCC) development was not precisely declared. CD47 mediates immune escape and macrophage phagocytosis of tumors. CDK4 mediates oncogenesis. Synergistic implications of TRPM8, CD47, and CDK4 in HCC were not declared. This research aims to demonstrate the expressions of TRPM8, CD47and CDK4 in HCC and to declare correlations and significance. Paraffin blocks from 101 hCC and 82 adjacent non-tumorous liver were immunostained using TRPM8, CD47 and CDK4 antibodies. HCC showed highly significant increased TRPM8, CD47, and CDK4 expressions than control liver tissue (p < 0.001) for all. TRPM8, CD47, and CDK4 were significantly associated with poor prognostic criteria as high tumor grade, advanced stage, microvascular invasion, and necrosis. There was a significant association between cirrhotic and non-cirrhotic adjacent liver regarding positive TRPM8 (p < 0.02) and high CDK4 expressions (p < 0.045). There were significant direct relationships between each immunohistochemical antibody and the other two. Prolonged overall survival was significantly associated with low CDK4 (p = 0.019). In conclusion, TRPM8, CD47, and CDK4 may regulate synergistic functions in HCC oncogenesis and accomplish unfavorable prognostic significance. TRPM8 and CDK4 might share in development of HCC from cirrhosis. TRPM8, CD47, and CDK4 could be therapeutic targets in HCC.