الفهرس 
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Abstract
SUMMARY
H
epatocellular carcinoma is the fifth most common cancer and the third leading cause of cancer related-deaths worldwide. More than 700,000 new cases are diagnosed each year throughout the world and also unfortunately more than 600,000 deaths are attributed to HCC each year.
HCC is usually asymptomatic in the early stages and tends to be invasive. The coexistence of inflammation and cirrhosis makes the early diagnosis and prognostic assessment of HCC much more difficult.
According to the national institute of cancer (NIC) in Egypt, HCC is considered to be one of the common malignancies in Egypt (It is the 2nd most common cancer site among males and 7th among females) as a normal result of the high prevalence of hepatitis B and C infection, as it represents about 45.3% of the new cases of the digestive system cancer.
The diagnosis of HCC is mainly based on a combination of abdominal U/S and serum AFP level. However, small tumors will be missed by abdominal U/S, moreover, serum AFP estimation lacks tumor specificity and has low sensitivity particularly in early stage disease. Clearly, the available screening methods are inadequate for early detection and follow up of HCC and hence, there is an urgent need for novel biomarkers to increase the sensitivity in early diagnosis of HCC as well as the specificity in differentiation between HCC and benign lesions.
Annexin A2 (ANXA2) is a 36 kDa calcium and phospholipid binding cytoskeletal protein of the Annexin superfamily. It has four forms, including secrete, membrane-bound, cytoplasmic, and nuclear form. The human ANXA2 gene consists of 13 exons distributed over 40 kb of genomic DNA on the long arm of chromosome 15 (15q21).
There are many reports showing that ANXA2 is differentially expressed between normal and malignant tissue and potentially involved in tumor progression. Many studies highlighted the role of ANXA2 as a biomarker for various malignant tumors such as breast, lung, gastric, colorectal, pancreatic and liver.
In this regards, the present study aimed to evaluate the clinical utility of serum ANXA2 as a novel biomarker for HCC, and to compare its diagnostic performance to AFP; the current marker of HCC.
This study was conducted at Tropical Medicine Department of Ain Shams University Hospitals on 50 HCC patients (group I), 25 patients with liver cirrhosis (group II), in addition to 15 apparently healthy, HCV and HBV-seronegative subjects as control group (group III).
All individuals in this study were subjected to full history taking, thorough clinical examination, radiological investigations including abdominal U/S and CT scan, laboratory investigations including viral markers; HCV RNA by RT-PCR, HBsAg and HBcAb by ELISA, liver function tests; AST, ALT, serum bilirubin, serum albumin and prothrombin time, serum AFP in addition to serum ANXA2 assay by ELISA technique.
Serum AFP showed a highly significant increase between liver cirrhosis group and control group. Moreover, a highly significant increase was noticed in HCC group when compared to liver cirrhosis or control groups.
As regards serum ANXA2, the results of the present study showed highly significant increases in HCC patients, when compared to the cirrhosis patients on one hand, and control group on the other hand.
The clinical utility of AFP and ANXA2 in discriminating patients with HCC from those with liver cirrhosis was assessed by ROC curve analysis. This revealed that the best diagnostic cut-off value for AFP to discriminate HCC patients from cirrhosis was 19.8 ng/mL. This had a diagnostic sensitivity of 70%, specificity of 96%, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 61.5% and efficacy 78.7% with AUC of 0.822. As for of ANXA2, the best cut-off value was 18 ng/mL. This had a diagnostic sensitivity of 74%, specificity of 88%, positive predictive value 92.5%, negative predictive value 62.9% and efficacy 78.7% with AUC of 0.873.
Conclusion: Serum level of ANXA2 can be a good marker for HCC, with higher sensitivity and negative predictive values than AFP.