肝细胞性肝癌的细胞与患者血液表面增强拉曼光谱研究

Early screening for hepatocellular carcinoma (HCC) is closely related to human health, and a challenge urgent to be solved. Surface enhanced Raman spectroscopy (SERS), and especially self-developed SERS-membrane electrophoresis and SERS-electroporation methods were used to investigate HCC cells and blood of HCC patients in our study. Firstly, we will develop a SERS and cellulose acetate membrance electrophoresis (CAME) based method which is fast, simple and non-invasive for plasma proteins detection, expecting to solve the problem of misdiagnosis and missed diagnosis induced by alpha fetoprotein (AFP) based screening. Secondly, to establish a blood circulating tumor cell (CTC) model of HCC cell lines, then, integrate SERS- electroporation method with magnetic activated cell sorting (MACS) method to screen circulating tumor cells from CTC model and HCC patients..To the best of our knowledge, this is the first work that employs SERS based methods to directly detect the plasma proteins of HCC patients and HCC cells. And, our research results will make a good foundation both in experimental and theoretical aspect for the early noninvasive screening, prediction of recurrence and metastasis for HCC, having great academic significance and clinical value.

肝细胞性肝癌（HCC）早期筛查是与人们健康密切相关、亟待解决的挑战性难题。本项目基于表面增强拉曼光谱（SERS）技术，特别以自主开发的SERS-膜电泳和SERS-细胞电穿孔方法对HCC的细胞和患者血液开展研究。第一，开发一种快速SERS-膜电泳检测新方法，对HCC患者的血浆蛋白开展SERS研究，有可能解决单纯依赖甲胎蛋白（AFP）筛查HCC出现漏诊的问题。第二，建立血液循环HCC细胞模型，将SERS-细胞电穿孔方法与免疫磁珠细胞富集方法相结合，对血液循环HCC细胞模型和已发生血行远处转移的HCC患者血液循环肿瘤细胞（CTC）进行筛选。.本项目旨在建立一种针对HCC患者血浆蛋白和HCC细胞的SERS检测方法，为HCC的早期无损筛查及转移复发预测提供实验基础和理论依据，国内外未见报道，具有重要的学术意义和临床价值。

本项目对肝细胞性肝癌（HCC）的细胞与患者血液开展表面增强拉曼光谱（SERS）研究，开发了一种快速膜电泳-SERS方法，即正反向膜电泳-SERS方法，应用该方法对HCC患者（AFP 升高/不升高）、健康人的血浆开展 SERS 研究, 同时对SERS-细胞电穿孔方法进行优化，对肝癌细胞株和其他癌症来源细胞开展SERS 研究。已发表研究论文24 篇，其中SCI –II区以上论文13篇。申请或获得授权发明专利10 项。获得授权7项，包括一项美国发明专利授权。项目组成员还获得2016 年福建省自然科学二等奖1项。