过往研究显示食管鳞癌早期患者5年生存率高于中晚期患者近10倍，然而目前只有15%的患者能够获得早期确诊，因此迫切需要更有效的早期诊断方法。近年发现肿瘤细胞能分泌大量含有非编码RNA（ncRNA）的外泌体到血循环中，检测循环外泌体内异常ncRNA分子为肿瘤早期诊断提供了新机遇。本课题将使用高通量测序、数字PCR技术和独特的数据分析方法通过病例-对照研究发现食管鳞癌相关的血浆外泌体长链ncRNA （lncRNA）及miRNA；通过观察早期食管鳞癌手术前/后血浆外泌体lncRNA/miRNA谱的变化验证有关ncRNA分子的特异性；用病例-对照研究探讨食管鳞癌特异性的外泌体lncRNA/miRNA谱早期诊断价值；最后通过体外实验探讨特异lncRNA/miRNA分子对食管鳞癌细胞表型及基因表达谱的影响，阐明其分子机制。本研究将为发现食管鳞癌新的早期诊断分子标记物，为揭示其分子发病新机制提供科学依据。

Previous studies indicate that the five-year survival rate for patients with early-stage esophageal squamous cell carcinoma (ESCC) is approximately 10 times higher than that for those with late-stage ESCC. Presently, however, only 15% of ESCC patients can be diagnosed at early stage. Thus, there is an urgent need to identify better method for early diagnosis. Recently, it has been found that tumor cells can release exosomes that contain non-coding RNAs (ncRNAs) into the blood. Investigation of aberrant circulating exosomal ncRNAs may provide new opportunity to discover tumor-related biomarkers. In this study, we will use next-generation sequencing、 digital PCR techniques、unique statistical approaches, and case-control study design to screen for and identify ESCC-associated plasma exosomal ncRNAs, specifically long ncRNAs (lncRNAs) and miRNAs. Then, we will compare the pre/post operation exosomal lncRNA/miRNA profiles in an independent cohort of early stage ESCC patients, to validate the specificity of ESCC-associated circulating exosomal ncRNA markers. We will further investigate the specificity and sensitivity of ESCC-specific exosomal ncRNA profiles for diagnosis of ESCC, using case-control study samples. Lastly, we will study the functional significance of specific ncRNAs in ESCC cell lines. This study will provide new insights into the molecular mechanisms of ESCC and identify novel biomarkers for early diagnosis of ESCC.