الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 168 |  |  |
| | | from | 168 | | |
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. HCC, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis.
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.
It was found that DGCR5 was significantly down-regulated in HCC tissues compared with that in adjacent non-tumor tissues. HULC was markedly up-regulated in HCC and is associated with its molecular pathogenesis.
The current study was carried out at Medical Biochemistry &Molecular Biology and Clinical Oncology &Nuclear Medicine Departments, Faculty of Medicine, Menoufia University.
The aim of this work is to study the role of DGCR5 and HULC LncRNAs relative expression levels in hepatocellular carcinoma.
This study involved 160 individuals, 70patients with HCC, and 90 apparently healthy subjects served as the control group.
All subjects recruited in this study underwent a standard procedure consisting of detailed history, complete physical examination, clinico-pathological data collection for HCC patients and relative quantification of DGCR5 and HULC LncRNAs relative expressions, using real time PCR technique.
The results of the present study can be summarized as follows:
There was high significant statistical difference between the two studied groups as regards smoking and HCV infection.
There was significant statistical difference between the two studied groups regarding serum creatinine, total bilirubin, Albumin, ALT, AST and AFP levels.
There was highly significant statistical increase of HULC relative expression level in HCC group when compared to control group, while there was significant statistical decrease of DGCR5 relative expression level in HCC group when compared to control group.
There was highly significant statistical increase of HULC relative expression level in stage IV when compared to stage I& II and III, while there was significant statistical decrease of DGCR5 relative expression level in stage IV when compared to stage I& II and III.
There was significant statistical increase of HULC relative expression level in HCC group as regards: PVT, portal hypertension, metastatic site (to bone compared with localized tumor, lung compared to either bone or localized tumor), child score (score B compared with score A and score C compared with score A).
There was significant statistical increase of HULC relative expression level in HCC group as regards: age, serum creatinine, total bilirubin, Albumin, ALT, AST and AFP levels.
There was significant statistical decrease of DGCR5 relative expression levels in HCC group as regards: PVT, portal hypertension, metastatic site (to bone compared with localized metastasis, to lung when compared also with localized metastasis) and child score (score B compared with score A and score C compared with score A).
There was significant statistical decrease of DGCR5 relative expression level in HCC group as regards: age, total bilirubin, serum albumin, AST and AFP levels.
For HULC; ROC curve analysis indicated that the best cutoff point to differentiate between HCC cases and controls was 1.50 with area under the curve of 0.914. The sensitivity, specificity, PPV, NPV and over all accuracy at this cutoff point were 82.9%, 100%, 100%, 88.2% and 92.5% respectively.
For DGCR5; ROC curve analysis indicated that the best cutoff point to differentiate between HCC cases and controls was 0.98 with area under the curve of 0.807. At this cutoff the sensitivity, specificity, PPV, NPV and over all accuracy was 61.4%, 100%, 100%, 76.9% and 83.1% respectively.
For AFP; ROC curve analysis indicated that the best cutoff to differentiate between HCC cases and controls was 217.5 with area under the curve of 1. At this cutoff the sensitivity, specificity, PPV, NPV and over all accuracy was 82.9%, 100%, 100%, 88.2% and 92.5%respectively.