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Novel Biomarkers For The Enhanced Detection O f Hepatocellular carcinoma

Novel Biomarkers For The Enhanced Detection O f Hepatocellular carcinoma . Motawa E El-houseini ＊ , Mohammed S. Mohammed ＊ , Wael M Elshemey , Tarek D Hussein, Omar S Desouky, and Anwar A Elsayed *NCI and Faculty of science,Cairo University. Primary Liver Cancer.

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Novel Biomarkers For The Enhanced Detection O f Hepatocellular carcinoma

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  1. Novel Biomarkers For The Enhanced Detection Of Hepatocellular carcinoma Motawa E El-houseini＊, Mohammed S. Mohammed＊, Wael M Elshemey, Tarek D Hussein, Omar S Desouky, and Anwar A Elsayed *NCI and Faculty of science,Cairo University

  2. Primary Liver Cancer • Hepatocellular carcinoma (Hepatocyte). • Cholangio Carcinoma (Cholangiolar cell). • Hemangio Sarcoma (Endothelial cell). • Perisinusoidal Cell Sarcoma (Perisinusoidal cell).

  3. Hepatocellular Carcinoma (HCC) • HCC is an extremely prevalent malignancy that is the fifth world wide. It is an important contributor to the mortality of those with chronic liver diseases in both developing and developed countries as well. • HCC is a multifactorial in origin. Several factors may develop HCC. • In Egypt: HCC contributes about 2.3% of all cancers with median age of 53 years and a male predominance of 5:1 (El-Bolkaiy 1998).

  4. Major Risk factors • Hepatitis B virus infection (80% of HCC ) • Hepatitis C virus infection (15-20% of HCC) • Exposure to Aflatoxin (AFB1) • Use of oral contraceptive steroids • Cigarette smoking

  5. Investigated Biochemical Markers • 1. Alpha feto protein [AFP] • 2. Alpha L-Fucosidase enzyme [AFU] • 3. Vascular endothelial growth factor [VEGF] • 4. VEGF-A • 5. Insulin like growth factor-II [IGF-II]

  6. Table(4.14.) Sensitivity, specificity, diagnostic accuracy and positive and negative predictive values for the investigated markers at their optimal cut-off values

  7. Fig.(4.10.) Receiver operating characteristic (ROC) curves for investigated markers: (A) AFP, (B) AFU, (C) VEGF, (D) VEGF-A and (E) IGF-II.

  8. Sensitivity of AFP (68%), AFU (82%) and VEGF-total (86%) in diagnosis of HCC in cirrhotic patients. The simultaneous use in diagnosis increased the sensitivity significantly (98%) 2% 98%

  9. Conclusion(1) • It has been possible to improve the detection of HCC by measuring the serum levels of combined biochemical markers. • AFU and VEGF are the best of the investigated markers to be combined to AFP in order to increase the sensitivity of HCC detection up to 98%. • The possibility of distinguishing cirrhosis, as a high-risk group, from HCC offers a hope for the early detection of HCC. The present results suggest a possible applied biochemical markers in the screening of HCC in order to detect the malignancy in an early and treatable stage.

  10. Promissing Novel Biomarkers for HCC First : Early Detection and Diagnosis--Alpha-L-fucosidase(AFU) enzyme system • -It is a lysosomal enzyme acting on A-Lfucose conjugated compounds Mainly glycoproteins and glycolipids. -A-L- fucose is 6-deoxy A-L galactose the latter is the epimer of glucose -Liver is the main site of galactose metabolism. -There are two simple ,rapid and not expensive methods for this enzyme assay.

  11. Second PrognosisVEGF -It is a potent angiogenic promotor via stimulation of endothelial proliferation. -It is a dimeric polypeptide with M.Wt.35-43KD.,localized to chom.6p12. -It occurs in family; VEGF-A ,B,C ,D &E., these share sequence structural homology to the primary family member.The genes for VEGF-B&C are localized to chrom.11q13 and chrom 4q34 respectively. -VEGF receptors are being tyrosine kinase type (FLK1 & FLT1 ).

  12. Clinical importance of VEGF -Sera level of VEGF are signficantly elevated in patients with HCC. ,compared to those benign liver lesions& cirrhosis as well as normal healthy subjects. -The level of VEGF in a pre-therapeutic stage appears to reflect its potential biological activity in term of invasion and metastasis. -Targeting VEGF Receptors for the future of anti-angiogenic therapy as targeted biological cancer therapy. • In non-HCC patients e.g.pediatric tumor -(Ewing sarcoma,Osteosarcoma, Neuroblastoma and Rhabdomyosarcoma) S.VEGF levels were found to be a good prognostic biomarker for therapeutic responsiveness

  13. Conclusion (2) -AFU could be an usefull biomarker in the early detection of HCC. -AFU in combination with AFP could incease the sensitivity from 68% to 98% for the detection of HCC -VEGF could be a good biomarker for prognosis of HCC as well as non-HCC Patients. -AFU,VEGF and AFP in a simultaneous combination could enhance the sensitivity for detection of HCC. ( 68% to about100% )

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