miR-483-5p作为乙肝病毒双突变(1762T,1764A)株感染者肝癌高危标记物的前瞻性研究

Hepatocellular carcinoma (HCC) is the first most common cancer in Guangxi. It threatened to the health and life of in local inhabitant. Most of them were at advanced stage when diagnosed and not suitable for treatment. Surveillance can detect HCC at an earlier stage and increase chance of treatment. However, population-based HCC surveillance programmes would place huge demands on public health resources and be impractical. To identify for surveillance the population at highest risk of HCC may reduce the cost of regular screening. However, currently, there is no ideal biomarker for identifying population at high risk of developing HCC...Cooperation with England, we established in 2004 a cohort of HBsAg-positive study subjects in Long An county. Within this cohort, we were the first to show that the double mutations (1762T, 1764A) in the hepatitis B virus (HBV) basal core promoter (BCP) are a valuable biomarker for identifying a subset of HBsAg carriers aged ≥30 at extremely high risk of developing HCC. With this biomarker, the number identified with HBsAg for surveillance may be reduced, at least by one half. Last year, cooperation with American, we found that serum miR-483-5p is a potential biomarker to differentiate between those who do and do not develop HCC, among individuals infected with HBV with BCP double mutations, using a case-control study. If so, the number for surveillance may be narrowed down greatly...Taking the unique advantage of our Long An cohort, we proposed to carry out a prospective study with purpose to verify the findings above. The relative expression of serum miR-483-5p will be measured using qRT-PCR. The data will be analysed using Poisson regression and ROC curve. The results will provide not only scientific basis for HCC accurately surveillance but also a clue to study the mechanisms of oncogenesis of miR-483-5p and so guide new strategies for prevention and control of HCC.

肝癌是广西第一大恶性肿瘤，严重威胁人们健康和生命。肝癌发现时多为晚期、无法治疗。监测可发现早期肝癌，提高治疗机会，而全人群监测费用大，无法实施，先找出肝癌高危人群再监测可降低成本，但目前无理想的肝癌高危标记物。.2004年我们与英国合作在隆安县建立了HBsAg无症状携带者研究队列，前瞻性研究证实乙肝病毒(HBV)双突变是30岁以上HBsAg无症状携带者肝癌高危标记物，使以HBsAg为标记物的监测人数至少减半。去年我们与美国合作用病例对照研究发现血清miR-483-5p可能是HBV双突变株感染者肝癌高危标记物，如获证实，监测人数可再大幅减少。.为验证此发现，本项目将利用隆安队列独有优势开展前瞻性研究，用qRT-PCR检测血清miR-483-5p表达量，用泊松回归和ROC曲线分析资料。研究结果不仅能为实现肝癌精准监测提供科学依据，且将启迪研究miR-483-5p致癌机理，为肝癌防治提供新思路。

肝癌是广西第一大恶性肿瘤，严重威胁人们健康和生命。肝癌发现时多为晚期、无法治疗。监测可发现早期肝癌，提高治疗机会，而全人群监测费用大，无法实施，先找出肝癌高危人群再监测可降低成本，但目前无理想的肝癌高危标记物。2004年我们与英国合作在隆安县建立了HBsAg无症状携带者研究队列，前瞻性研究结果证实乙肝病毒(HBV)双突变是30岁以上HBsAg无症状携带者肝癌高危标记物，使以HBsAg为标记物的监测人数至少减半。2017年，我们与美国合作用病例对照研究发现血清miR-483-5p可能是HBV双突变株感染者肝癌高危标记物，如获证实，肝癌监测人数可再大幅减少。.为此，本项目利用隆安队列独有优势开展前瞻性研究，用qRT-PCR检测研究对象血清miR-483-5p表达量，探索miR-483-5p与肝癌危险性关系，查明miR-483-5p 肝癌诊断阈值有无动态变化，探索miR-483-5p能否作为肝癌早期诊断指标。.研究结果发现，459名研究对象3年半期间有32名发生肝癌，发病率为1991.9/100,000人年。miR-483-5p可作为感染HBV BCP双突变株人群肝癌高危标记物，肝癌组miR-483-5p血清表达量显著高于对照组（P=0.003），表达量在取值为2.0倍时，HBV BCP双突变株感染人群肝癌相对危险度（RR）为3.13；受试者工作特征曲线（ROC曲线）下面积(AUC)为0.727，在取值为2.2697倍时，诊断敏感性为62.5%、特异性为32.6%，当AFP单独应用时，AUC为0.684，敏感性为37.5%、特异性为99.5%；当miR-483-5p和AFP联合应用时，AUC为0.904，可显著提高AFP诊断肝癌效能。多数肝癌患者发病前1-2年血清miR-483-5p表达量已开始出现升高，随后出现高、低波动，联合AFP，可作为肝癌早期诊断参考指标。.本研究培养了1名博士研究生、2名硕士研究生，已发表2篇SCI期刊收录的文章，与主要研究成果有关的论文仍在撰写中。.本研究成果为肝癌高危人群筛查提供了新的标记物，将使肝癌监测人数再大幅减少，节省巨大的监测费用。成果的应用还可弥补AFP敏感性低的不足，提高AFP肝癌诊断效能。因此，本研究成果不仅能为实现肝癌精准监测、提高诊断效能提供科学依据，而且将启迪研究miR-483-5p致癌机理，为肝癌防治提供新思路。

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