Overexpression of Heat Shock Protein HSP90AA1 and Translocase of the Outer Mitochondrial Membrane TOM34 in HCV-induced Hepatocellular Carcinoma: A Pilot Study

Objective: Identification of new molecular markers to enhance early diagnosis, prognosis and/or treatment of hepatocellular carcinoma (HCC) is a need. TOM34 (34 kDa-translocase of the outer mitochondrial membrane) protein expression deregulation has demonstrated to be involved in the growth of many cancers. Here, we aimed at evaluating serum TOM34 and some heat shock proteins (HSPA4, HSPA1B, and HSP90AA1) expressions in hepatitis C virus (HCV)-related cirrhosis and HCV-induced HCC relative to controls and correlating these expressions to the clinicopathological data.

Methods: Serum specimens were collected from 90 patients with HCV associated complications (30 cirrhotic, 30 early HCC and 30 late HCC) and 60 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the four target genes using the Livak method. In silico network analysis was also executed to explore the contribution of the genes in liver cancer.

Results: The serum TOM34 and HSP90AA1 transcripts were significantly upregulated in HCC patients compared to cirrhotic ones with more up-regulation in late HCC patients. Receiver operating characteristic analysis showed the optimum cutoff value of 0.625 corresponding to 71.7% sensitivity and 56.7% specificity, and an area under the curve (AUC) of 0.705 to discriminate HCC from cirrhotic groups (P = .002). In multivariate analysis, ordination plot showed obvious demarcation between the study groups caused by the higher levels of TOM34 among other variables.

Conclusions: TOM34 and its partner HSP90AA1 might be used as a potential biomarker for monitoring HCV-induced HCC progression in the Egyptian population. Future large-scale validation studies are warranted.