Association of Polymorphism in MicroRNA 604 with Susceptibility to Persistent Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma

Abstract

MicroRNA polymorphisms may be associated with carcinogenesis or immunopathogenesis of infection. We evaluated whether the mircoRNA-604 (miR-604) polymorphism can affect the persistence of hepatitis B virus (HBV) infection, and the development to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 subjects, who have either past or present HBV infection, were enrolled and divided into four groups (spontaneous recovery, chronic HBV carrier without cirrhosis, liver cirrhosis and HCC). We genotyped the precursor miR-604 genome region polymorphism. The CC genotype of miR-604 rs2368392 was most frequently observed and T allele frequency was 0.326 in all study subjects. The HBV persistence after infection was higher in those subjects with miR-604 T allele (P=0.05 in a co-dominant and dominant model), which implied that the patients with miR-604 T allele may have a higher risk for HBV chronicity. In contrast, there was a higher rate of the miR-604 T allele in the chronic carrier without HCC patients, compared to those of the HCC patients (P=0.03 in a co-dominant model, P=0.02 in a recessive model). The T allele at miR-604 rs2368392 may be a risk allele for the chronicity of HBV infection, but may be a protective allele for the progression to HCC in chronic HBV carriers.Graphical Abstract

Polymorphisms in the precursor microRNAs and aflatoxin B1‐related hepatocellular carcinoma

“…These data suggest that the miR-1268a rs28599926 polymorphism should be an important genetic susceptible factor of cancer risk. Noticeably, previous studies have shown that rs11614913 (located in miR-196a-2), and rs2620381 (located in miR-627) modify the risk of some tumors such as colorectal cancer, lung cancer, and liver cancer [18,35,36]. Supporting aforementioned risk role, our report also exhibited that these two polymorphisms affected HCC risk, although there was no statistical significance observed according to the threshold of test power.…”

“…For example, in 2011, Zhang et al reported that rs11614913 and rs2910164 (located in miR-146a) did not affect HBV-related HCC risk [17]. Another recent report by Cheong et al [18] has shown that rs2368392 (located in miR-604, SNP19) increases susceptibility to persistent HBV and ultimately may increase HBV-related HCC. Our present study exhibited this polymorphism was not correlated with AFB1-HCC risk.…”

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…These results encourage future studies on the potential role of MALAT1 in CCA. In addition, increased levels of miR-604 and miR-551B in serum EVs from patients with CCA also provided excellent diagnostic capacities (up to 0.944) for CCA and some studies already started to evaluate their involvement in carcinogenesis and as diagnostic biomarkers [87][88][89][90]. Considering the high resistance of small ncRNAs to RNase degradation, additional efforts should be employed in order to validate their diagnostic accuracy.…”

ORN: Extracting Latent Pathway Activities in Cancer with OR-gate Network

“…As for the results in the METABRIC dataset, upstream modules of six latent pathways were almost identical and hence merged into one union (pathway 0, 1, 2, 7, 9, 14 in supplement (28) and the metastasis of colorectal cancer (29). MIR604 was differentially expressed in breast cancer (30).…”