الفهرس 
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Abstract
Hepatocellular carcinoma is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis. It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol or aflatoxin.
Although they can be small and slow growing, HCC tumors can be successfully treated by aggressive surgery, patients often lose the window for surgical resection due to the lack of effective tools for early diagnosis which results in very low 5-year survival rates. Therefore, to improve the prognosis of HCC, it is important and critical to develop specific and sensitive diagnostic biomarkers for HCC.
Non coding RNAs play important regulatory roles in the development and progression of many diseases including cancers. Several studies showed that some lncRNAs were up-regulated or down-regulated in HCC and associated with its molecular pathogenesis.
The aim of this study is to detect if there is an association between Expression of some long non coding RNAS (LNCRNAs) as (RAMS11, LINC01564), CBX4, and TOP2A and clinical; pathological characteristic of hepatocellular carcinoma in Egyptian patients.
The current study was carried out by cooperation between, chemistry department, faculty of science, Menoufia University, Molecular biology and Medical Biochemistry, Clinical Oncology and Internal Medicine Departments, Faculty of Medicine, Menoufia University in the period from December 2021 to May 2022.
The study was conducted on 150 subjects classified into 3 groups: group I: 50 patients with Hepatocellular carcinoma, group II: 50 patients with chronic Hepatitis C, group III: apparently healthy control subjects.
The results of the present study can be summarized as follows:
Sex and age were insignificantly different among the three groups
ALT and AST Total Bilirubin and direct bilirubin were significantly increased in HCC and HCV compared to control group (P value <0.001)
platelet count, Hb and serum albumin was significantly decreased in HCC and HCV compared to control group (P value <0.001)
α FP was significantly increased in HCC compared to HCV and control groups (P value <0.001), HCV was significantly increased compared to control groups
There was insignificant difference between HCC and HCV groups in Loss of weight, Jaundice, Hepatic Encephalopathy, Splenomegaly and Comorbidities.
Ascites and Child Pugh Class was significantly decreased in HCC compared to HCV group
Long noncoding RNAs (Linc01564, RAMS11), CBX4, and TOP2A were significantly different among the three groups. All were
significantly higher in HCC group compared to HCV and control groups (P value <0.001) and significantly higher in HCV group compared to control group.
(LINC01564, RAMS11), CBX4, and TOP2A can significantly discriminate HCC patients from HCV group (P <0.001) with high sensitivity and specificity for each of them. The power of the relative expression levels of lncRNA to diagnose CHC among studied subjects was evaluated using ROC analysis The relative expression level of lncRNA (LINC01564, RAMS11) CBX4, and TOP2A was positively correlated in HCC group with ALT, AST and overall survival time, on the other hand were insignificantly correlated with age, Hb, platelets, WBCS, serum albumin, total bilirubin, direct bilirubin, PT and α FP.
LINC01564 was significant higher in patients with LN metastasis than patients without LN metastasis (P value 0.032). LINC01564 and CBX4 were significant higher in patients with IV stage tumor than those with I, II and III stage tumors and patients with BCLC stage C tumor than patients with B stage tumor (P value= 0.007, <0.001, =0.001, <0.001 respectively). However, they were significantly lower in alive patients (P value <0.001, 0.002) respectively. On the other hand,there were insignificant difference among CBX4, LINC01564 and other parameters ( vascular invasion, abdominal pain, tumor numbers, tumor size, tumor site, gender, loss of Weight, Jaundice ,Hepatic Encephalopathy, splenomegaly, Ascites, Comorbidity, Child Pugh Class and Bilharziasis ). Regarding Top2A and RAMS11, they had the same results as CBX4, LINC01564.
In univariate regression analysis, total bilirubin, direct bilirubin, α FP, BCLC(C), CBX4, RAMS11 were significant predictors for mortality. In multivariate regression analysis, LN metastasis, LINC01564 and TOP2A were independent predictor for mortality (P value= 0.044, HR= 13.077(1.065 – 160.525)) and (P value= 0.038, HR= 1.544(1.024 – 2.329)) respectively.