Abstract
BackgroundMiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.MethodsWe conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment.ResultsThe variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81–1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59–0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele.ConclusionsThese findings indicate that rs1076064 may be a biomarker for HCC susceptibility and prognosis through altering pri-miR-378 transcription.
Highlights
Hepatocellular carcinoma (HCC) is a major cancer burden in China [1]
The demographic characteristics of the 1300 hepatocellular carcinoma (HCC) cases with positive Hepatitis B virus (HBV), 1344 HBV carriers and 331 intermediate or advanced HCC cases were summarized in Table S1 in File S1
For the 331 HCC patients in stage B or C retained in our survival analysis, 258 died from HCC, and 2 died from other causes during a period up to 60.7 months of follow-up
Summary
Hepatocellular carcinoma (HCC) is a major cancer burden in China [1]. Hepatitis B virus (HBV) infection has been well established as a major risk factor in HCC carcinogenesis [2]. Previous studies have demonstrated that genetic factors play important roles in the progression of HCC, including chemosensitivity, tumor recurrence and prognosis [6,7,8,9,10]. MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis
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