الفهرس 
H. DiagnosisOnly 14 pages are availabe for public view
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Abstract
Liver cancer is the sixth most common cancer and the third cause of cancer related deaths. In Egypt, hepatocellular carcinoma (HCC) has become the second most prevalent cancer among men.
Detailed analysis & characterization of molecular, genetic & epi-genetic events would revolutionize early diagnosis of HCC.
Gene & protein expression profiling will allow better screening of different stages of HCC as well as establishment of criteria for targeted therapies.
The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene against activated oncogenes.
Downregulation of RECK is documented in a wide range of malignant neoplasms (e.g. pancreatic cancer, breast cancer…etc.) and correlates with poor prognosis & tumor metastasis.
The aim of this work was to study the association between RECK gene polymorphism and the development of hepatocellular carcinoma in patients with liver cirrhosis.
This study was conducted on 115 individuals. The patients were recruited from outpatient clinic and/or inpatient Department of Hepatology, Gastroenterology & Infectious Diseases, Benha faculty of Medicine, and from the outpatient clinic of the National Research Center.
Summary
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They were divided into three groups: group I comprised 47 patients with HCC diagnosed by ultrasonography and triphasic computed tomography (CT), group II comprised 48 patients with cirrhosis diagnosed by clinical, laboratory, ultrasonographic examination and liver biopsy whenever possible, and group III comprised 20 healthy volunteers as controls.
In the current study, HCC was more common in males than females with a ratio 3.7:1. Patients with HCC had a mean age of 60.8 years with a range of 48-89 years.
Both HCC and cirrhosis were more common in urban areas than rural areas (63.8% and 79.2% respectively). Also, HCC and cirrhosis were more common in non-farmers than farmers (66%).
HCC was more common in smokers than none smokers (51.1%). None of all the cases were alcoholics
Regarding the medical history of the studied groups, abdominal pain and abdominal enlargement are the most prominent symptoms in HCC patients (74.5% and 70.2% respectively). Jaundice, weight loss, disturbed conscious level were more common in HCC patients than cirrhotic patients. History of blood transfusion was higher in HCC patients than cirrhotic patients. While history of operations was more common in cirrhotic patients than HCC patients.
Manifestations of hepatocellular decompensation was present in both HCC and cirrhotic patients, yet some features (such as jaundice, palmar erythema, astrexis, fetor hepaticus, and lower limb oedema) were more evident in HCC patients than cirrhotic patients.
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Most HCC patients had shrunken liver (93.6%) followed by enlarged liver (6.4%) while none had average liver. Only 23.4% of HCC patients had hard liver consistency while the rest of HCC patients had firm liver (76.6%). Ascites was a more common finding in HCC patients than cirrhotic patients. Splenomegaly was more common in HCC patients than cirrhotic patients.
HCV was presumably the main etiology of liver cirrhosis in both groups.
Abdominal ultrasound examination showed that nearly half of the HCC patients (51.1%) had average liver, followed by shrunken liver (40.4%). Cirrhosis was present in all patients (group I and II). 42.6% of HCC patients showed heterogeneous liver echotexture, and 14.9% of HCC patients had lymph node enlargement on ultrasound. Splenomegaly, portal vein thrombosis and ascites were more commonly found in HCC patients than cirrhotic patients. Focal lesions were mainly single in 51.1% of HCC cases, mainly seated at the right lobe in 55.2% of cases.
Child grade C cases were significantly higher in HCC patients than cirrhosis patients; where most cases of HCC was Child grade C rather than Child grades A and B. Child grade A cases were significantly higher in cirrhotic group than HCC group, where most of cirrhotic patients were Child A, followed by Child C, then Child B.
HCC cases showed significantly higher mean value for MELD and uMELD scores than cirrhotic cases.
CT scan of HCC group showed that cirrhosis was present in 100% of cases with HCC, focal lesions were mainly solitary (51.1%), more in Right lobe, portal vein thrombosis was present in 17% of cases. Splenomegaly was present in most of HCC patients (93.6%), also ascites was found in (72.3%) of HCC patients.
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Laboratory test showed that the mean values fasting blood glucose and serum creatinine were significantly higher in HCC patients than cirrhotic patients. On the other hand, total leucocytic count was higher in HCC patients, platelet count was lower in HCC patients than cirrhotic patients, while no difference was found between the two groups as regards hemoglobin concentration.
AST and AFP were significantly higher in HCC patients than cirrhotic patients. ALT was higher in HCC than cirrhotic patients but this was not statistically significant. The mean value of albumin was significantly lower in HCC patients than cirrhotic patients, but the mean value of INR and total bilirubin were higher in HCC patients with no statistical significant difference between the groups.
As regards the staging systems of HCC, most HCC patients were Okuda stage III (48.9%), CLIP stage II (48.9%), VISUM stage I (44.7%) and advanced Tokyo stage (57.5%).
RECK gene rs10814325 polymorphism analysis was done in the three studied groups; where the wild type was T/T, and the mutant types were T/C and C/C. HCC was more prevalent (55.3%) in mutant RECK genotypes (T/C and C/C) than the wild RECK genotype T/T (44.7%). Contrary to cirrhotic patients and healthy controls, where the majority of them were of the wild T/T RECK genotype (77.1% and 95% respectively).
As regards the wild T/T RECK genotype, the highest percentage was found in the healthy control group (95%) followed by the cirrhotic group (77.1%) and lastly the HCC group (44.7%). The difference was statistically significantly between HCC patients and cirrhotic patients (p=0.001), also between HCC patients and healthy controls (p=0.001).
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Regarding the mutant T/C RECK genotype, the highest percentage was found in the HCC group (53.2%) followed by the cirrhotic group (22.9%) and lastly the healthy control group (5%). Also, a significant difference was found between HCC and cirrhotic patients (p=0.002) as well as HCC patients and healthy controls (p=0.0002).
Only one case of mutant C/C RECK genotype was found in the HCC group (2.1%), none were found in neither the cirrhotic group, nor the healthy control group.
Assessment of the relation between RECK genotypes and the severity of liver disease due to cirrhosis in HCC patients revealed that the mean value of MELD score in the mutant genotype T/C was significantly higher than that of the wild type T/T and the mutant type C/C (p=0.03). On the other hand, no statistically significant difference was found between the three genotype subgroups as regards UMELD score (p=0.2).
Regarding Child A class, a significant difference was found between the wild T/T group and the mutant T/C groups (p=0.04). No significant difference was found between the wild T/T and mutant C/C groups, nor between the mutant T/C group and C/C groups. No significant differences were found between the three genotype groups as regards Child B and Child C classes.
The 3 RECK gene subgroups of HCC were compared to the radiological findings as regards the liver size, liver heterogenicity, portal vein thrombosis, presence of ascites, splenomegaly and lymph node involvement. No statistical significance was found as regards all these radiological findings.
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No specific pattern of association was found between the 3 RECK genotypes and the focal lesions in HCC patients as regards the focal lesion diameter or the number of focal lesions.
Assessment of the relation between RECK genotypes and the different staging systems in HCC patients showed that only Okuda stage 1 patients had a significant difference between the wild T/T and the mutant C/C groups (p=0.05), also between the mutant T/C and the mutant C/C groups (p=0.0004). No significant difference was found between the three genotype groups as regards Okuda stage 2 and 3, CLIP staging system, VISUM staging system as well as Tokyo score.
Receiver operator characterizing (ROC) curve was done to determine the sensitivity and specificity of RECK gene polymorphism analysis in both HCC patients and control group, it yields low sensitivity (55.3%), high specificity (95%), the AUC is 0.752 with a statistically significant p-value (0.001).
Also, ROC curve of RECK gene polymorphism analysis in HCC and cirrhosis patients, yields a low sensitivity (55.3%), moderate specificity (77.1%), with a statistically significant p-value (0.006) and an AUC of 0.664