Lipocalin: A Novel Diagnostic Marker for Hepatocellular Carcinoma in Chronic Liver Disease Patients in Egypt

Abstract

Hepatocellular carcinoma is one of the most prevalent life-threatening human cancers with etiological factors chronic viral hepatitis B and C infections. Tumor cell dispersion relies on the loss of homotypic cell-cell adhesion. Invasion through basement membrane and interstitial extracellular matrix is another key event for metastatic progression, which requires the action of a series of proteolytic enzymes named matrix metalloproteinases, secreted by tumor cells that enhance tumor invasiveness and metastasis. TIMPs are dominant inhibitors of MMPs and able to control MMP-mediated ECM breakdown by binding active forms of MMPs. Lipocalin-2 is known as neutrophil gelatinase associated lipocalin promotematrix degradation and tumor progression. Aim : To evaluate the importance of lipocalin for diagnosis HCC in Egyptian chronic liver disease patients. Subjects and Methods : 50 patients and 25 controls. (G-1) 25 HCC on top of hepatitis C. (G-2) 25 hepatitis C. The following done: schistosoma antibodies, ASAM, LKM-1, ANA AKA and CBC. Hepatitis B surface antigen, Hepatitis C antibodies AFP, Cupper and zinc, Matrix metaloprotinase-9, TIMP-1 and Neutrophil gelatinase-associated lipocalin. Results : Median value of MMP-9 level in G-I (206 μg/L) is significantly higher than G-2 (100 μg/L) and G 3 (49 μg/L) p < 0.001. TIMP-9 median value G-1 (48 μg/L) is significantly lower than G-2 (54 μg/L) and G-3 (113 μg/L) p < 0.001. Lipocalin-2 median levels are significantly higher in G-I (389 ng/mL) than G-2 (166 ng/ml) versus G-3 (60 ng/mL) p < 0.001. Lipocalin-2 associated with increasing lobular inflammation, ballooning & fibrosis with MMP-9 has an important role in pathogenesis of liver cirrhosis and HCC. Conclusion : We elucidated predictive value for MMPs, TIMPs, and progression metastasis of hepatocellular carcinoma. Liver cell impairment alters metabolism of trace metals as zinc and copper, with possible relationship of these changes to pathogenesis of chronic liver disease. Lipocalin-2 can be used as a future diagnostic marker with better sensitivity and specificity than MMP-9 for the progression of hepatocelluar carcinoma.