The i̇nvestigation of micrornas as potential biomarkers in serum and tissue for hepatitis b virus related hepatocellular carcinoma

Hepatocellular carcinoma (Hepatocellular Carcinoma; HCC) accounts for 90% of primary liver cancer and is the fifth most common cancer and the second cause of cancer-related death in the worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for HCC development. microRNAs (miRNAs) are highly preserved small non-coding RNAs of 22 nucleotides in length, which modulate gene expression at the post-transcription level, affecting both stability and translation of complementary mRNAs. Since miRNAs show significant stability under conditions such as low pH and resistance to RNAase, it has shown that it can be used as a new potential biomarker for early detection of HCC. The aim of this study is to investigate of microRNAs as potential biomarkers in serum and tissue for hepatitis B virus related hepatocellular carcinoma. Between March 2016-December 2019, the expression levels of miR-21-5p, miR-122a-5p, miR-182-5p, miR-221-5p and miR-223-5p in serum and tissue samples from 35 HCC patients, 35 chronic HBV patients (CHB), and 30 healthy individuals were analyzed by quantitative real-time PCR test (miScript SYBR® Green PCR Kit, Qiagen, Germany). Serum miR-21-5p, miR-122a-5p, miR-182-5p and miR-221-5p expression levels were found to be upregulated in patients with HCC compared to the CHB and control group, while serum miR-223-5p expression level were downregulated in patients with HCC compared to the CHB and control group. While tissue miR-21-5p, miR-182-5p and miR-221-5p expression levels were upregulated in patients with HCC compared to the CHB and control group, the tissue miR-122a-5p and miR-223-5p expression levels were downregulated. In the diagnostic evaluation of serum expression levels found statistically significant in patients with HCC compared to the control group by ROC (Reciever Operator Characteristic Curve; ROC) analysis, miR-21-5p AUC (Area Under Curve; AUC) value of 0.763, miR-122a 5p AUC value of 0.819, miR-221-5p AUC value of 0.721 and miR 223-5p AUC value of 0.801 were detected. In the diagnostic evaluation of tissue expression levels found statistically significant in patients with HCC compared to the control group by ROC analysis, miR-21-5p AUC value of 0.801, miR-122a-5p AUC value of 0.629, miR-221-5p AUC value of 0.706 and miR-223-5p AUC value of 0.560 were found. In conclusion, the serum and tissue expression levels of miR-21-5p, miR-122a-5p, miR-221-5p and miR-223-5p, which differentiate HCC from CHB and healthy individuals with accuracy, have been shown to be used as potential biomarkers in the early diagnosis and prognosis of HCC patients. Serum and tissue expression levels of these miRNAs can be used as an indicator of the progression of CHB to cirrhosis and HCC.