ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the leading cause of cancer mortality. Various studies have linked dysregulated microRNA expression to liver cancers, but those related to viral hepatitis-related HCC are limited. METHODS: We investigated the diagnostic and prognostic roles of circulating miR-331-3p, miR-23b-3p, and miR-3194-5p in EDTA-treated blood samples of 50 hepatitis C virus (HCV) HCC patients, 50 HCV cirrhotic patients, and 50 healthy controls using quantitative real-time polymerase chain reaction. RESULTS: We found that miR-23b-3p and miR-3194-5p were significantly downregulated, whereas miR-331-3p was upregulated in HCC patients compared with controls. Also, these miRNAs were significantly dysregulated in HCC compared with cirrhotic patients. For the diagnosis of HCC, miR-331-3p and the combined miRNAs panel had the highest area under the curve (AUC), followed by miR-3194-5p. The highest AUC for differentiating metastatic from nonmetastatic patients was shown by miR-331-3p and the combined miRNAs panel, followed by miR-23b-3p. Dysregulation of miRNAs was associated with poor clinicopathological manifestations. Finally, miR-331-3P was found to be an independent risk factor for metastatic lesions in HCC. CONCLUSION: Overall, the assessed miR-331-3p, miR-23b-3p, and miR-3194-5p were significantly associated with poor clinicopathological features of HCC and could be used to discriminate HCV-related HCC patients from cirrhosis and differentiating metastatic from nonmetastatic patients, primarily miR-331-3p along with combined miRNAs. Moreover, miR-331-3p was found to be an independent factor for metastatic lesions.
ABSTRACT
BACKGROUND: The high mortality rate of hepatocellular carcinoma (HCC) in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection (HCV) and late diagnosis of the carcinoma. MicroRNAs (miRNA), which regulate tumor proliferation and metastasis in HCC, may serve as a useful diagnostic approach for the early detection of HCC, thus decreasing its mortality. Meanwhile, endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes. AIM: To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters. METHODS: We compared levels of endocan and circulating miRNA 9-3p from 35 HCV-related HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls recruited from inpatient and outpatient clinics of the National Liver Institute, Menoufia University, Egypt in the period from January to March 2021 in a case-control study. Serum samples from all groups were analyzed for HCV. Endocan was measured by enzyme-linked immunosorbent assays, and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR. RESULTS: The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups, while levels in the chronic liver disease were significantly lower than those in the control group (P < 0.001). The levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups. Moreover miRNA 9-3p and endocan performed better than α-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients. The levels of miRNA 9-3p were significantly inversely correlated to vascular invasion (P = 0.002), stage of advancement of Barcelona Clinical Liver Cancer (P < 0.001) and the metastatic site (P < 0.001) of the HCC group. CONCLUSION: Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.
ABSTRACT
Exposure to benzene is a common occupational hazard as well as a hematopoietic system intoxicant, but the entire picture of its molecular pathogenesis is still hazy. Its leukemogenic effect could be attributed to DNA damage, decreased repair capacity, altered methylation patterns, and defective apoptosis. Poly ADP-ribose polymerase1, DNA methyltransferase1, and CCCTC-binding factor (PARP1-DNMT1-CTCF) complex play an essential role in methylation maintenance and DNA damage repair response. This study aimed to assess the expression of PARP1, PAR glycohydrolases (PARG), DNMT1, CTCF, and apoptosis-inducing factor (AIF) in subjects occupationally exposed to benzene. A total of 200 subjects were enrolled in this study: 100 workers occupationally exposed to benzene (painters and decorators) and 100 unexposed office workers. Occupational exposure data were obtained. The biochemical and hematological evaluations were done. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess mRNA expression of PARP1, PARG, DNMT1, CTCF, and AIF. Both biochemical and hematological parameters were within normal limits; workplace benzene air concentration was significantly higher in exposed workers than the levels among controls (P < 0.001). Significant decrease in mRNA levels of PARP1, DNMT1, CTCF, and AIF was noticed among the exposed group (P = 0.01, P < 0.001, P = 0.004, P < 0.001, respectively) in comparison with the control group, while PARG showed non-significant difference (P = 0.16). There was a significant negative correlation between workplace benzene air concentration and expression levels of PARP1, DNMT1, and AIF. The reduced expression of PARP1, DNMT1, CTCF, and AIF observed in exposed workers may represent one of the first benzene-induced changes that might threaten erythropoiesis.
