Acta Oncol Tur.. 2014; 47(2): 1-7 | DOI: 10.5505/aot.2014.02886

Priority of Alpha-L- Fucosidase Over Alpha fetoprotein in Early Detection of Hepatocellular Carcinoma in Animals and Human

Nabil Mohie Abdel Hamid¹, Maiada Hasan Nazmy², Bakheet Elkot Moustafa³, Sahar Mohamed Saad El-din^2
1Department Of Biochemistry, Faculty Of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
²2department Of Biochemistry, Faculty Of Pharmacy, Minia University, Minia, Egypt.
³Department Of Biochemistry, Faculty Of Pharmacy, Al-azhar University, Assiut, Egypt.

OBJECTIVE: Early detection of hepatocellular carcinoma (HCC) is the most critical step in the management process. We try to provide new insights about the possible role of alpha-L- fucosidase (AFU) to achieve more reliable detection of HCC over a classical marker alpha fetoprotein (AFP).
METHODS: The study included both animal and human subjects, to legislate our theory. In animal study, 60 Male Wistar rats were classified to control, other 3 groups received di ethyl nitrosamine (DENA) for 8, 16, 24 weeks respectively. In human study: one hundred and twenty patients were assigned as: control group, 3 groups with histologically graded HCC, into mild, advanced and metastatic HCC. Histological and biochemical analysis (AFP, AFU, liver function tests, total antioxidant serum levels) in both animals and patients, as well as, receiver operating characteristic (ROC) curves and correlation analysis, were executed.
RESULTS: DENA-treated groups showed significant histopathological changes in a time dependant pattern. After 24 weeks, a significant variation in biochemical parameters (AFP,AFU, liver function tests and total anti-oxidant serum levels), after 6 weeks, a significant variations in all parameters except bilirubin and total antioxidants, after 8 weeks, a significant variations in all parameters except bilirubin, albumin, AFP and total antioxidants, compared to control group. All tested biochemical parameters showed non-significant correlation, compared to AFU.
All histologically-graded human HCC groups showed a highly statistically significant variations in all tested biochemical parameters. ROC analysis showed that at a cut-off value of 5 μmol/l/min, AFU yielded a sensitivity and specificity of 90% and 92%, respectively producing diagnostic accuracy of 91%. While At a cut-off value of 60 ng/ml, AFP yielded a sensitivity and specificity of 60% and 76%, respectively producing diagnostic accuracy of 68%. Correlation coefficients between AFU versus ALT, AST and AFP were statistically significant

CONCLUSION: AFU is a more accurate marker than AFP for early diagnosis of HCC. AFU showed higher sensitivity, specificity and correlated more to other indices than AFP. Human data confirmed our theory.

Keywords: Hepatocellular carcinoma (HCC), Diethylnitrosoamine (DENA), Alpha-L-Fucosidase, Alpha-fetoprotein, Liver indices, antioxidant status, Early detection

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Hayvan ve Ýnsanlarda Hepatosellüler Karsinomun Erken Teþhisinde Alfa-L Fukosidaz’ýn Alfa-fetoproteine olan Üstünlüðü

Nabil Mohie Abdel Hamid¹, Maiada Hasan Nazmy², Bakheet Elkot Moustafa³, Sahar Mohamed Saad El-din^2
1Eczacýlýk Fakültesi Biyokimya Anabilim Dalý, Kafrelsheikh Üniversitesi, Kafrelsheikh, Mýsýr
²Eczacýlýk Fakültesi Biyokimya Anabilim Dalý, Minia Üniversitesi, Minia, Mýsýr
³Eczacýlýk Fakültesi Biyokimya Anabilim Dalý, El-ezher Üniversitesi, Assiut, Mýsýr

AMAÇ: Erken taný hepatoselüler karsinom (HCC) tedavisindeki en kritik adýmdýr. Çalýþmada erken tanýda alfa-L- fukosidazýn (AFU) klasik belirteç olan alfa-fetoproteine (AFP) kýyasla güvenilirliði incelenmiþtir.
YÖNTEMLER: Teorimizi kanýtlamak için çalýþma hem insan hem de hayvan örneklemler kullanýlacak þekilde planlanmýþtýr. Çalýþmanýn hayvan deneyi ayaðýnda 60 Wistar faresi kontrol grubu ve 8, 16, 24 hafta dietilnitrozamine (DENA) verilen gruplar olmak üzere 4 gruba ayrýlmýþtýr. Ýnsan çalýþma grubu kontrol ve hafif, ileri ve metastatik olarak 4 gruba bölünen toplam 120 hastadan oluþmaktadýr. Histolojik ve biyokimyasal analizler (AFP, AFU, karaciðer fonksiyon testleri, total antioksidan serum seviyeleri) ve ROC eðrileri ile korelasyon analizleri insan ve hayvan gruplarýnda yapýlmýþtýr.
BULGULAR: DENA-tedavi grubu zamana baðlý olarak belirgin histopatolojik deðiþiklikler göstermiþtir. Kontrol grubu ile kýyaslandýðýnda 6 hafta sonra bilirubin ve total antioksidanlar dýþýndaki tüm biyokimyasal parametrelerde, 8 hafta sonra bilirubin, albumin, AFP ve total antioksidanlar dýþýndaki parametrelerde ve 24 hafta sonra ise tüm biyokimyasal parametrelerde (AFP, AFU, karaciðer fonksiyon testleri ve total antioksidan serum düzeylerinde) anlamlý deðiþiklikler saptanmýþtýr. Histolojik olarak sýnýflandýrýlmýþ tüm HCC gruplarýnýn tün incelenen parametrelerinde istatistiksel olarak anlamlý sonuçlar saptanmýþtýr. Sýnýr olarak 5 μmol/l/min kabul edildiðinde ROC analizi ile yapýlan incelemede AFU %90 sensitivite, %92 spesifite göstermiþtir ve %91 tanýsal doðruluk göstermiþtir. Sýnýr deðer 60 ng/ml olarak alýndýðýnda ise sensisivite, spesifite ve tanýsal doðruluk sýraýyla %60, %76 ve %68 olarak saptanmýþtýr. AFU ile ALT, AST ve AFP iliþki katsayýlarý istatistiksel olarak anlamlýdýr.
SONUÇ: HCC erken tanýsýnda erken tanýda AFU, AFP’den daha iyi bir belirteçtir. AFU sensitivite, spesivitesi daha yüksek olup diðer indekslerle AFP’ye kýyasla daha iyi korele olmuþtur. Ýnsandan elde edilen sonuçlar teorimizi doðrulamýþtýr.

Anahtar Kelimeler: Hepatoselüler karsinom, Dietilnitrozamine; Alpha-L-fucosidase; Alpha-fetoprotein; Antioksidan seviyesi; Erken taný

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