基于外泌体microRNAs的液体活检探讨“治未病”在股骨头坏死超早期诊断中的应用

osteonecrosis of the femoral head (ONFH), a deliberating disease, usually affects the young adult which poses a heaven burden to society and economy. Femoral head usually collapses which is irreversible stage due to no effective methods to diagnose it in early stage. Therefore, it is very necessary to detect ONFH as early as possible which happens to meet the theory of "preventive treatment of disease". Liquid biopsy consisting of exosomal microRNAs is non-invasive way characterizing with stability and specificity. As bio-markers, exosomal microRNAs has been widely used in diagnosing many kinds of diseases including cancers in their early stage. However, there is rare data about exosomal microRNAs in diagnosing ONFH. Our study aims to ①analyse the exosomal microRNAs expression from the serum of the healthy and ONFH patients using Illumina Hiseq2500 platform, try to find significantly experssed miRNAs (potential bio-markers) ②validate "potential bio-markers" with q-PCR and MRI in high risk ONFH patients, try to identify bio-markers in super early diagnosing ONFH as well as support the objective parameter(s) for the theory of "preventive treatment of disease".

股骨头坏死(ONFH)是好发于中青年的高致残性疾病，造成了沉重的社会和经济负担。由于缺乏有效的早期诊断手段，发现时大多数股骨头已发生不可逆的改变(塌陷)，因此尽早发现ONFH尤为重要，这也是“治未病”的体现。以外泌体microRNAs（exosomal miRNAs）为代表的液体活检属于非介入性检查，具有活性稳定、敏感度高等特点，已广泛应用于包括癌症等多种疾病的超早期诊断，但在股骨头坏死诊断中的应用尚未见报道。本课题拟：①通过Illumina Hiseq2500测序平台，对比正常人、ONFH病人血清外泌体miRNAs的表达信息，寻找ONFH中明显表达异常的miRNAs作为潜在标志物；②结合q-PCR、MRI在ONFH高危人群中验证潜在标志物，尝试确定用于ONFH诊断的生物标志物，旨在借助无创技术超早期发现ONFH，客观化体现“治未病”理论。

股骨头坏死(ONFH)是好发于中青年的高致残性疾病，造成了沉重的社会和经济负担。由于缺乏有效的早期诊断手段，发现时大多数股骨头已发生不可逆的改变(塌陷)，因此尽早发现ONFH尤为重要，这也是“治未病”的体现。以外泌体microRNAs为代表的液体活检属于非介入性检查，已广泛应用于多种疾病的超早期诊断，但在股骨头坏死诊断中尚未报道。本课题①通过Illumina Hiseq2500测序平台、生物信息学、q-PCR等技术，对比、验证正常人、ONFH病人血清外泌体miRNAs的表达信息，发现并确定了一组明显表达差异的外泌体microRNAs，例如：hsa-miR-486-5p，hsa-miR-242-5p等，十分具有超早期诊断ONFH的潜在价值；②结合核磁共振影像技术，在不同时间段随访，发现在ONFH高危病人中hsa-miR-206异常高表达并与ONFH的发生、发展有关。通过本课题的研究，我们尝试确定了用于ONFH诊断的生物标志物，该类标志物具有超早期发现ONFH的应用潜能，同时为客观化体现“治未病”理论提供了现代医学证据。