Affiliations: [a] Department of Biochemistry, University of Karachi, Karachi, Pakistan | [b] The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, Pakistan | [c] Department of Molecular Genetics, Dr. Ziauddin Hospital, Karachi, Pakistan
Correspondence:
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Corresponding author: Rizma Khan, Department of Molecular Genetics (DMG), Dr. Ziauddin University Hospital, Karachi 75700, Pakistan. Tel.: +92 331 274 6801; E-mail: [email protected].
Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancer in the world and a reason behind different oncogenes activation and tumor suppressor genes inactivation. Hyper-methylation of tumor suppressor genes including RASSF1a, GSTP1, p16, and APC cause gene silencing as well as tumor cell invasion. STAT 1 gene is a part of signaling cascade of JAK/STAT and any dysregulation in signaling has been implicated in tumor formation. OBJECTIVE: The current investigation focus on the methylation role of STAT1 gene as a non-invasive biomarker in the progression and diagnosis of hepatocellular carcinoma. METHODS: STAT1 gene methylation status in 46 HCV induced hepatocellular carcinoma patients and 40 non-HCC controls were examined by methylation specific PCR. STAT1 gene expression was examined by real time PCR and further validated by various bioinformatics tools. RESULTS:STAT1 methylation in HCV-induced HCC (67.4%) was significantly higher compared to the non-HCC controls (p< 0.01). However, mRNA expression of STAT1 gene in methylated groups was significantly lower compared to unmethylated groups (p< 0.05). Furthermore, insilco analysis of STAT1 validated our results and shown expression of STAT1 mRNA was lower in liver cancer with the median 24.3 (p= 0.085). CONCLUSION: After using peripheral blood samples we observed that STAT1 silencing caused by aberrant methylation could be used as potential non-invasive biomarker for the diagnosis of HCV induced hepatocellular carcinoma. We conclude that blood as a sample source could be used instead of biopsy for early detection of HCC.
Keywords: Hepatocellular carcinoma, STAT1, cancer biomarker, methylation, CpG Island
