Heat shock protein 60 and chromatin assembly factor-1 mRNA levels in hepatitis C virus-related hepatocellular carcinoma and clinical significance

Abstract

Background: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Heat Shock protein 60 (HSP60), a mitochondrial chaperone, is overexpressed in diverse malignant cells. Chromatin Assembly Factor-1 (CAF-1), a histone chaperone, is down-regulated in quiescent non-proliferating human cells. We aimed to clarify the role of HSP60 and CAF-1 mRNA expression in diagnosis of HCC post-HCV infection.Methods: HSP60 and CAF-1 mRNA levels in urine and blood were quantified by Taqman real-time PCR in 49 subjects; 25 cirrhotic with HCV-related HCC, 12 cirrhotic without HCC and 12 healthy controls.Results: HSP60 and CAF-1 mRNA levels in urine and blood were significantly higher in HCC versus cirrhosis and controls, and in cirrhosis versus controls. Their levels in HCC were significantly increased by advancement of HCC BCLC staging system. HSP60 in urine had 85% sensitivity and 66% specificity at cut off 258354 RU and 85% sensitivity and 60 % specificity at cut off 37576 RU in blood for HCC diagnosis. CAF-1 in urine had 81% sensitivity and 66% specificity at cut off 137756 RU and 77% sensitivity and 64% specificity at cut off 49726 RU in blood for HCC diagnosis. HSP60/CAF-1 sensitivity and specificity in urine and blood were better than either marker alone, with better results in urine (91% and 73%, respectively) than blood (88% and 66%, respectively).Conclusions: HSP60 and CAF-1 in urine and blood may be useful HCC diagnostic markers that were correlated with advancement of HCC with better combined marker sensitivity and specificity than either marker alone especially for urine.