Background Circulating microRNAs (miRNAs) have been shown to dysregulate in many cancer types including hepatocellular carcinoma (HCC). The purpose of this study was to examine the potential diagnostic or prognostic roles of circulating miRNAs in patients with hepatitis B virus (HBV)-related HCC. Methods Paired cancerous and adjacent non-cancerous liver tissue specimens of patients with HBVrelated HCC were used as a discovery set for screening 800 miRNAs by a Nanostring quantitative assay. Differentially expressed miRNAs were then examined by SYBR green quantitative RT-PCR in a validation cohort of serum samples obtained from 70 patients with HBVrelated HCC, 70 HBV patients without HCC and 50 healthy controls. Results The discovery set identified miR-223-3p, miR-199a-5p and miR-451a significantly lower expressed in cancerous tissues compared with non-cancerous tissues. In the validated cohort, circulating miR-223-3p levels were significantly lower in the HCC group compared with the other groups. The combined use of serum alpha-fetoprotein and miR-223-3p displayed high sensitivity for detecting early HCC (85%) and intermediate/advanced stage HCC (100%). Additionally, serum miR-223-3p had a negative correlation with tumor size and BCLC stage. On multivariate analysis, serum miR-223-3p was identified as an independent prognostic factor of overall survival in patients with HCC. In contrast, circulating miRNA-199a-5p and miR-451a did not show any clinical benefit for the diagnosis and prognostic prediction of HCC.
Circulating lnc RNAs have attracted considerable attention as potential noninvasive biomarkers for diagnosing cancers. RT ‐ qPCR is the canonical technique for detecting circulating RNA and depends largely on stable reference genes for data normalization. However, no systematic evaluation of reference genes for serum lnc RNA has been reported for cervical cancer. Here, we profiled and validated lnc RNA expression from serum of cervical cancer patients and controls using microarrays and RT ‐ qPCR . We identified lnc RNA RP 11‐204K16.1, XLOC _012542, and U6 small nuclear RNA as the most stable reference genes based on geNorm, NormFinder, BestKeeper, delta Ct, and RefFinder. These genes were suitable also for samples from different age groups or with hemolysis. Additionally, we discovered lnc RNA AC 017078.1 and XLOC _011152 as candidate biomarkers, whose expression was down‐regulated in cervical cancer. Our findings could aid research on circulating lnc RNA and the discovery of blood‐based biomarkers for cervical cancer diagnosis.
Background The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated. Methods A total of 101 HCV GT1-infected patients (65 monoinfection and 36 HIV coinfection) who received EBR/GZR for 12–16 weeks were included. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured by transient elastography. Serum HCVcAg was measured in parallel with HCV RNA. Results The overall SVR12 and SVR24 rates in the cohort were 98.0% and 95.0%, respectively. SVR24 rates were consistently high (90.0% to 100%) across all subgroups of patients. A significant LS decline ≥30% was observed more frequently in cirrhotic than non-cirrhotic individuals who achieved SVR (63.3% versus 30.3%; P=0.003). The magnitude of LS decline following HCV eradication was comparable between HCV monoinfection and HCV–HIV coinfection. The reduction of CAP was also observed in responders who had significant steatosis at baseline. Compared with HCV RNA, HCVcAg testing displayed high sensitivity (100%) and specificity (99.0–100%) in determining SVR12 and SVR24. Conclusions This study confirms that EBR/GZR is effective for HCV GT1-infected Thai patients with or without HIV infection. HCV eradication is associated with LS and CAP improvement regardless of HIV status. HCVcAg testing could be a potential replacement for HCV RNA for assessing SVR in resource-limited settings.
MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.
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