International Journal of Clinical Medicine, 2013, 4, 440-450 http://dx.doi.org/10.4236/ijcm.2013.410079 Published Online October 2013 (http://www.scirp.org/journal/ijcm) Lipocalin: A Novel Diagnostic Marker for Hepatocellular Carcinoma in Chronic Liver Disease Patients in Egypt Hoda Aly Abd El Moety 1 , Rania Mahamed El Sharkawy 1 , Nevin Abd El Menem Hussein 2 1 Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt; 2 Applied Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt. Email: hodaabdelmoety@yahoo.com Received July 13 th , 2013; revised August 15 th , 2013; accepted September 10 th , 2013 Copyright © 2013 Hoda Aly Abd El Moety et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 en- hance 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 Egyp- tian 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 ge- latinase-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 pre- dictive 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. Keywords: Lipocalin-2; MMP-9; TIMP-1; Cu; Zn; HCC 1. Introduction Hepatocellular carcinoma (HCC) is one of the most pre- valent life-threatening human cancers that is not only increasing in worldwide incidence in the past decade [1- 4], but also a leading cause of cancer-related deaths world- wide [3-6]. HCC is an aggressive and enigmatic disease, which represents approximately 85% of liver cancers [5,6]. The most prominent etiological factors associated with HCC consist of chronic viral hepatitis B and C in- fections [4,7-9], nonalcoholic fatty liver disease [10-12], and toxin and alcohol exposure [6,9]. The development and progression of HCC is a multistep and long-term process characterized by the progressive sequential evo- lution of morphologically distinct preneoplastic lesions (formed as a result of chronic liver injury, necro-in- flammation and regeneration, small cell dysplasia, low- grade and high grade dysplastic nodules) that culminates in the formation of HCC [5,13]. Dispersion of tumor cells from the primary tumor is considered one of the key events for metastatic progres- sion. Tumor cell dispersion relies on the loss of homo- typic cell-cell adhesion, which is largely mediated by E- cadherin/catenin complex [14]. Invasion through base- ment membrane and interstitial extracellular matrix is another key event for metastatic progression, which re- quires the action of a series of proteolytic enzymes named matrix metalloproteinases (MMPs) [15,17]. MMPs are a group of zinc-dependent endopeptidases that share Copyright © 2013 SciRes. IJCM