Glycoregulatory Enzymes as Early Diagnostic Markers during Premalignant Stage in Hepatocellular Carcinoma

摘要

Hepatocellular carcinoma (HCC) is the third leading cause of death and fifth most common malignancy worldwide. Objective: Present study focused on the abnormal tumor cell glucose metabolism, considering the pathways of hexose monophosphate (HMP) shunt enzymes. The key regulatory enzymes of HMP include hexokinase (HK), glyeraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate dehydrogenase (G6PD). Their perturbations sought to be helpful in the diagnosis and prognosis of HCC in addition to alpha-fetoprotein (AFP). Materials and methods: Diethyl nitrosamine (DENA) plus carbon tetra chloride (CCl4) chemically-induced HCC model was used. Sixteen male albino rats were equally divided into 2 groups. Group I: served as a normal control received single intraperitonial (I.P) injection of saline, 2 weeks later, received subcutaneous (S.C) injection of saline, in equal volumes given for group II animals. Group II animals received single I.P injection of DENA (200mg/kg), 2 weeks later, received S.C injection of CCl4 (3ml/Kg/week) for 6 weeks. Then animals were sacrificed, blood and liver samples were obtained. Results: In HCC group, relative liver weights, serum AFP and HK, GAPDH and G6PD activities in both serum and liver homogenate were significantly increased; subsequent decrease in body weight was also evident. The histopathological examination of liver biopsies revealed the presence of few dysplastic nodules. Such nodules were 1mm or more in diameter on macroscopic examination, indicating carcinogenic features, nuclear and cytoplasmic alterations with clustering of population cells, structurally abnormal portal tracts, supporting serum enzyme and tumor marker assays. Conclusion: Glycolytic alterations can be used for diagnosis and prognosis of carcinogenesis in liver. These biomarkers may be beneficial tools to improve diagnostic performance of conventional tumor markers as AFP.