The role of aurora kinase A in HBV-related hepatocellular carcinomas. Molecular and immunohistochemical study

Aim: Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with Hepatitis B Virus (HBV) among its major risk factors. Cryptogenic hepatocellular carcinoma (KR-HCC) refers to HCC that is clinically and serologically unrelated to an etiology. The Aurora Kinase A (AURKA) gene is overexpressed in many types of cancer. In our study, in HBV-associated HCC (HBV-HCC) and CR-HCC cases, AURKA gene amplification and expression level, as well as the efficiency of AURKA, its substrates P53Ser315, PLK-1Thr210 and BRCA1 were investigated. Material and Method: In the study, each group was represented by 17 cases; It was designed as HBV-HCC (Group I), KR-HCC (Group II) and Control group (normal liver tissue) (Group III). In the study, AURKA gene copy number change (gene-KSD) and expression level were examined by molecular methods. In addition, the effectiveness of AURKA on its substrates P53Ser315, PLK-1Thr210 and BRCA1 was investigated by immunohistochemical method (IHC). Results: When Group I and Group II were compared with the Control group (Group III), no significant difference was found in terms of gene-KSD (p=0.060). AURKA level was high in Group I-Group II and the difference between Group III was significant (p<0.001). P53 Ser315 was higher in both HCC groups (p<0.001), PLK-1Thr210 was higher in Group II (p=0.001), BRCA1 was higher in Group I (p=0.006), and the difference between the control group and them was statistically significant. Conclusion: Overexpression of AURKA was observed in HBV-HCC and CR-HCC cases. PLK-1, whose activity was increased by AURKA-mediated phosphorylation, was found to be highly expressed in CR-HCC cases, and BRCA1 in HBV-HCC cases. The results demonstrated the importance of developing different approaches and strategies for HBV-HCC and KR-HCC in therapies targeting the inhibition of substrates BRCA1 and PLK-1 with AURKA. Keywords: Aurora Kinase A, PLK-1, Hepatocellular carcinoma, HBV-related HCC, Cryptogenic HCC