同一个体食管/贲门双源癌和癌前病变基因组变异特征谱对比研究

Under the support by the NSFC on CC cancer projects and other projects, we have established the esophageal and cardia cancer and intraepithelial neoplasm database, including 500 thousands for ESCC and GCA, 25 thousands for CC and 13 thousands for the patients with concurrent intraepithelial precancerous lesions from the esophagus and gastric cardia. The detailed medical records and pathological information have been collected for all the patients. One hundred and fifty thousands patients have been follow-up from 5 to 30 years. The tissue and blood sample bank has been established with a total of 200 thousands samples. With these projects, we have identified a group of novel proteins correlated with CC patients. To steer away the past insistence on exploring the novel proteomic alteration alone, the present study is designed to identify the key biomarkers to predict preciously the precancerous lesion progression to cancer by extracting the characteristic genomic spectrum and validation with large sample size for ESCC and GCA with the unique CC database and tissue bank with whole exome sequencing. To correlate the clinical phenotypes and genotypes through whole genomic sequencing and whole exome sequencing and target region sequencing, the present project will provide important technical support for accurate diagnosis and treatment of ESCC and GCA. We are sure to obtain the promising biomarkers to predict the precancerous lesion progression to cancer if the application could be approved, because of that we have set up excellent database and biobank, and more importantly, we have a very unique research group focused on esophageal and gastric cardia cancer research.

在国家杰青和二项双源癌面上基金项目等支持下，本项目组历20年已建立50万例食管和贲门癌及2.5万例同一个体食管贲门双源癌（CC）和1.3万例双发癌前病变患者的诊疗、病理和随访数据库及20万例血和组织样本库，发现一组CC特异蛋白。双源癌和双发癌前病变发生在同一个体，遗传和环境因素相似，是甄别癌前病变进展和食管/贲门癌基因组特征谱差异的理想模型。本项目一改以往偏重发现CC患者特异相关蛋白的思路，利用双源癌和癌前病变独特病例资源优势和已建立的活检组织基因组外显子测序等技术，获得癌前病变进展及食管贲门癌基因组变异特征谱，揭示本项目组所发现的CC患者特异相关蛋白表达变化的分子基础及其与基因组变化的关系。本项目已拥有扎实的工作基础和最优团队，非常有信心通过本项目的实施，获得可用于食管和贲门癌前病变进展精准预测的关键候选分子标志物，为食管和贲门癌高危人群分子分型、预警筛查和早期发现提供重要分子靶标。

在国家杰青和二项双源癌面上基金项目等支持下，本项目组历20年已建立50万例食管和贲门癌及2.5万例同一个体食管贲门双源癌（CC）和1.3万例双发癌前病变患者的诊疗、病理和随访数据库及20万例血和组织样本库，发现一组CC特异蛋白。双源癌和双发癌前病变发生在同一个体，遗传和环境因素相似，是甄别癌前病变进展和食管/贲门癌基因组特征谱差异的理想模型。本项目通过对205例食管/贲门双源癌的食管癌组织、贲门癌组织和外周血DNA进行全基因组外显子测序发现食管癌相关高频突变基因47个，贲门癌相关高频突变基因83个，其中二者共有的高频突变基因11个。通过进一步目标区域测序，确定1个食管癌相关高频突变基因和12个贲门癌相关高频突变基因。本项目一改以往偏重发现CC患者特异相关蛋白的思路，利用双源癌和癌前病变独特病例资源优势和已建立的活检组织基因组外显子测序等技术，获得癌前病变进展及食管贲门癌基因组变异特征谱，揭示本项目组所发现的CC患者特异相关蛋白表达变化的分子基础及其与基因组变化的关系。本研究为食管癌和贲门癌高危人群分子分型、预警筛查和早期发现提供重要分子靶标。

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