Aim: We aimed to identify novel exosomal circular RNAs for hepatocellular carcinoma (HCC) diagnosis. Materials & methods: Exosomes were extracted and characterized. The expression level of exosomal circRNAs were verified via quantitative real-time PCR. The diagnostic value of candidate circRNAs was evaluated according to the receiver operating characteristic curve analysis. Results: The exosomal circ_0070396 significantly elevated in HCC patients than other control groups and it performed better in distinguishing HCC patients from healthy donors than that of α-fetoprotein. Combination of two above markers exerted greater diagnostic performance. Exosomal circ_0070396 could discriminate HCC individuals from patients with chronic hepatitis B and liver cirrhosis. Intriguingly, exosomal circ_0070396 was positively correlated with HCC progression. Conclusion: Exosomal circ_0070396 may be a potential biomarker for HCC detection and management.
Background:Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms (rs751402, rs873601, and rs2296147) with cancer risk.Methods:Pubmed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies in English and Chinese. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the association between XPG polymorphisms (rs751402, rs873601, and rs2296147) and cancer risk.Results:Twenty-three studies were included. Overall, there was no significant association between rs751402 polymorphism and overall cancer risk under the 5 gene models. However, we observed strong correlation between rs751402 polymorphism and gastric cancer (C vs T: OR=1.21, 95% CI = 1.00–1.26, P = .045; TC vs CC: OR = 1.12, 95% CI = 1.00–1.24, P = .041; TC/TT vs CC: OR = 1.13, 95% CI = 1.02–1.26, P = .020). There was a significant correlation between rs873601 polymorphism and cancer risk under the homozygous model (GG vs AA: OR = 1.16, 95% CI = 1.07–1.26, P = .001). Moreover, significant association with breast cancer was detected for rs873601 polymorphism under the allele contrast model (G vs A: OR = 1.10, 95% CI = 1.02–1.20, P = .021). In the subgroup of Asian, rs873601 polymorphism was related to the susceptibility to cancer (G vs A: OR = 1.07, 95% CI = 1.03–1.12, P = .010; GG vs AA: OR = 1.15, 95% CI = 1.06–1.26, P = .001; AG/AA vs GG: OR = 1.08, 95% CI = 1.01–1.15, P = .031; AA vs AG/GG: OR = 1.13, 95% CI = 1.05–1.21, P = .001). Significant association between rs2296147 polymorphism and cancer risk were observed in Asian population (CT vs TT: OR = 0.93, 95% CI = 0.87–0.99, P = .036).Conclusions:Our meta-analysis suggested that the rs873601 polymorphism was significantly associated with overall cancer risk. The moderate effects of rs751402 and rs2296147 polymorphism on cancer susceptibility might be highly dependent on cancer type and ethnicity, respectively. Large studies are needed to validate our findings, especially in Caucasian and African population.
Mouse double minute 4 (MDM4) is a p53-interacting oncoprotein that plays an important role in the p53 tumor suppressor pathway. The common rs4245739 A > C polymorphism creates a miR-191 binding site in the MDM4 gene transcript. Numerous studies have investigated the association between this MDM4 polymorphism and cancer risk, but have failed to reach a definitive conclusion. To address this issue, we conducted a meta-analysis by selecting eligible studies from MEDLINE, EMBASE, and Chinese Biomedical databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. We also performed genotype-based mRNA expression analysis using data from 270 individuals retrieved from public datasets. A total of 15 studies with 19796 cases and 49681 controls were included in the final meta-analysis. The pooled results revealed that the MDM4 rs4245739C allele is associated with a decreased cancer risk in the heterozygous (AC vs. AA: OR = 0.82, 95% CI = 0.73−0.93), dominant (AC/CC vs. AA: OR = 0.82, 95% CI = 0.72−0.93), and allele contrast models (C vs. A: OR = 0.84, 95% CI = 0.76−0.94). The association was more prominent in Asians and population-based studies. We also found that the rs4245739C allele was associated with decreased MDM4 mRNA expression, especially for Caucasians. Thus the MDM4 rs4245739 A > C polymorphism appears to be associated with decreased cancer risk. These findings would be strengthened by new studies with larger sample sizes and encompassing additional ethnicities.
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