炎症介导的EGFR由内而外调节肺腺癌侵润网络构建及对抗策略

项目名称： 炎症介导的EGFR由内而外调节肺腺癌侵润网络构建及对抗策略

项目编号： No.81501372

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 黄菊香

作者单位： 北京邮电大学

项目金额： 18万元

中文摘要： 本项目拟筛选不同于正常邻近组织的高表达肺腺癌中与表皮生长因子受体（EGFR），溶质运载蛋白家族2成员1（葡萄糖转运蛋白）（SLC2A1），透明质酸介导运动因子受体（HMMR），胞质分裂调控蛋白1（PRC1），泛素结合酶E2C（UBE2C）有激活关系的GRNInfer和Pearson相关系数（CC）≥0.25重叠的两两正相关分子，整合GRNInfer和GO，KEGG等知识库，构建其反馈和上下游单分子网络（分别与本网络分子有直接激活关系）；反向验证在肺腺癌正常邻近组织与EGFR、SLC2A1、HMMR、PRC1、UBE2C有直接抑制关系的GRNInfer和Pearson CC≤-0.25重叠的两两正相关分子中提取抑制假说的共同分子，建立并分析其共同分子在肺腺癌正常邻近组织的总激活反馈和上下游网络作为炎症介导的EGFR由内而外调节肺腺癌侵润对抗策略，为肺腺癌的整合诊断和治疗奠定基础并开辟新途径。

中文关键词： 信号传导；表皮生长因子受体；炎症诱导；肺腺癌侵润；对抗策略

英文摘要： In this project, different Pearson mutual-positive-correlation EGFR (epidermal growth factor receptor), SLC2A1 (solute carrier family 2 (facilitated glucose transporter) member), HMMR (hyaluronan-mediated motility receptor (RHAMM)), PRC1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin-conjugating enzyme E2C)-activatory molecular network will be constructed from overlapping of GRNInfer and Pearson under SLC2A1, HMMR, PRC1, UBE2C CC ≥0.25 in high lung adenocarcinoma compared with low human normal adjacent tissues, respectively. The EGFR inside-out activated inflammation-induced cell motility through SLC2A1-HMMR-PRC1-UBE2C single molecular feedback, upstream and downstream network (with direct-activated relationship to molecules of the network, respectviely) will be constructed in high lung adenocarcinoma, based on integrative GRNInfer with GO, KEGG, GenMAPP, BioCarta and disease databases. The Pearson mutual-positive-correlation inhibiting-hypothesis common molecules will be selected from the overlapping of GRNInfer and Pearson under EGFR, SLC2A1, HMMR, PRC1, UBE2C CC≤-0.25 in low human normal adjacent tissues different from high lung adenocarcinoma for reverse proofing our hypothesis. The inhibiting-hypothesis common molecular feedback, upstream and downstream total activatory network will be constructed in low human normal adjacent tissues as counter-strategy of EGFR inside-out activated inflammation-induced cell motility in lung adenocarcinoma. The project is very useful to develop a new route and identify novel markers and potential drugs for prognosis and therapy of lung adenocarcinoma.

英文关键词： signal transduction;epidermal growth factor receptor;inflammation-induced;lung adenocarcinoma motility;counter-strategy