الفهرس 
HEPATOCELLULAR CARCINOMAOnly 14 pages are availabe for public view
 |  | from | 283 |  |  |
| | | from | 283 | | |
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. The mortality of liver cancer worldwide is ranked as fourth between other cancer causes in males and females. In Egypt, it is a major problem due to the high prevalence of Hepatitis C Virus infection.
The occurrence and progression of HCC depends on many risk factors, but the main and most important risk is liver cirrhosis of any cause followed by hepatitis B, C, obesity, Non-alcoholic fatty liver disease (NAFLD) and aflatoxin.
The surveillance programs and diagnostic testing modalities for HCC in all guidelines depends on the radiological methods. The main serum biomarker used nowadays is the AFP although it has unfavorable sensitivity and specificity and its role is limited to screening. These were the main reasons that led researchers to look for new modalities of testing to diagnose HCC in early stages where radical treatment options can take the upper hand.
MicroRNAs are considered from the short non-coding RNAs. It can control the genetic material by affecting the mRNA of the gene at the post-transcriptional level or even affect the gene itself at the transcriptional level. It was also discovered that microRNA can stimulate (up-regulate) or inhibit (down-regulate) the target genes.
In addition, microRNA was found to have a great role and can be used in diagnosis of many tumors giving the chance for early non-invasive diagnostic methods.
In this study, our aim was to characterize the expression of the serum non-coding microRNA (miR-519d-3p) and the associated targeted gene SQSTM1 to evaluate their usefulness as diagnostic molecular biomarkers for HCC.
This study was conducted at Internal Medicine Department, Faculty of Medicine, Ain Shams University and it was approved by the Ethical Committee of Ain Shams University, Faculty of medicine.
The study included (50) participants from the Internal Medicine Department, Hepatology Unit, inpatients wards & outpatient clinic, divided into (34) HCC patients diagnosed according to American Association for the Study of Liver Diseases (AASLD) practice guidelines using multiphasic contrast-enhanced CT imaging, (11) chronic liver infection patients and (5) normal volunteers.
All subjects enrolled in the study were subjected to detailed history taking, full physical examination, laboratory investigations, including serum ALT, AST, serum albumin, serum bilirubin Total, direct, INR, viral markers as (HCV Ab, HBVs Ag) serum AFP and imaging studies which included pelvi-abdominal ultrasonography and triphasic contrast-enhanced CT imaging. In addition, quantitative real time polymerase chain reaction (qRT-PCR) were conducted on serum samples to detect the level and pattern for the microRNA (hsa-miR-519d-3p) and the mRNA of (SQSTM1) gene in HCC cases with or without hepatitis virus infections and compare it with the level in chronic liver infected cases and also with healthy personnel. All data were statistically analyzed. Results were compared to results of similar researches.
Our results showed that the serum level of miRNA (hsa-miR-519d-3p) is upregulated in the serum of Hepatocellular group in comparison with chronic liver infection group and the healthy group. These results were also seen with the serum level of mRNA (SQSTM1), as a significant upregulation of its serum level were detected in HCC group compared to the levels in chronic liver infection and healthy groups.
In addition to these results, the sensitivity and specificity of (hsa-mir-519d-3p), (mRNA of SQSTM1) in comparison to (AFP) was (91.2%-81.8%), (97.1%-100%) and (76.5%-72.7%) respectively. And the best cut off values of the three tests was (≥ 8.34) for miR-519d, (≥ 7.89) for mRNA SQSTM1 and (≥7.30) for AFP.
All these results showed that the serum microRNA (miR-519d) and the messenger RNA of (SQSTM1) gene as diagnostic tests of HCC, showed higher sensitivity and specificity than that of AFP, and accordingly it can be used in detecting early cases of HCC with better results.
In addition, we have identified that (hsa-mir-519d-3p) has upregulated its targeted gene (SQSTM1) and this upregulation is at the transcriptional level not at the post transcriptional level as it increased the mRNA level. This action of (mir-519d-3p) on SQSTM1 gene go with their actions as oncogenic microRNA and oncogenic gene in the progression of HCC.
CONCLUSION
This study concluded that the serum microRNA (hsa-mir-519d-3p) and the serum mRNA of its targeted gene (SQSTM1) are both significantly upregulated in the serum of Hepatocellular carcinoma (HCC) patients. And that the (hsa-mir-519d-3p) stimulates the gene (SQSTM1) at the transcriptional level. Finally, we could conclude that the serum microRNA (hsa-mir-519d-3p) and the serum mRNA of (SQSTM1) gene can be used as a diagnostic biomarker for HCC with good sensitivity and specificity even for early stages of HCC in comparison with AFP.
RECOMMENDATIONS
• Using the serum non-coding microRNA (hsa-miR-519d-3p) and the mRNA of its targeted gene SQSTM1 in the diagnosis of Hepatocellular carcinoma (HCC) even in its early stages. As they showed high sensitivity and high specificity in comparison to Alpha-feto protein (AFP).
• Further studies are needed to detect levels of (miR-519d-3p) and mRNA of (SQSTM1) gene pre & post various modalities of treatment to assess the ability of using it to monitor treatment response and for detection of recurrences.
• Multicentric studies with more variabilities to prove the reliability of serum microRNA (miR-519d-3P) and mRNA (SQSTM1) as diagnostic biomarkers of HCC.