肿瘤干细胞相关基因表达特征预测结直肠癌辅助化疗敏感性及复发风险

化疗耐药是导致结直肠癌术后肿瘤复发的重要原因。我们前期研究建立了一系列结直肠癌风险预测模型(Gastro 2019, 2018; CCR 2018), 早期发现高危患者并干预肿瘤进展在临床上有重要意义。肿瘤干细胞是引起化疗耐药、肿瘤复发的重要因素，本项目以肿瘤干细胞特征性基因为切入点，通过蛋白基因互作数据库，筛选基因靶点。进而利用表达谱数据库，通过生存分析筛选化疗预后基因，构建了10基因肿瘤干细胞特征预测模型，并在超过1000例的公共队列上进行验证。为进一步明确10基因预测模型的临床价值和分子机制，本项目拟在申请人参与的ICGC-ARGO结直肠癌课题中验证2000例中国人队列，结合多组学数据进行生物信息通路分析、网络分析和功能注释，并通过回顾性和前瞻性样本进行RT-qPCR验证。本研究将揭示影响结直肠癌患者肿瘤复发的关键基因及其功能，建立实用分子标记物，为临床治疗提供依据。

Chemotherapy resistance is believed to be one of the major reasons for the failure of cancer treatment strategies for colorectal cancer (CRC). Our previous study established a series of gene signatures for risk prediction in CRC (Gastroenterology 2019; Gastroenterology 2018; CCR 2018), and the early detection and timely intervention for high-risk patients are crucial for better clinical management. The cancer stem cell (CSC) is one of the primary factors in causing chemotherapy resistance and tumor recurrence. In this study, we first identified CSC related genes using protein-protein/gene interaction database as the initial candidates. Next, high-throughput gene expression profiles were used to select robust prognostic genes for patients with adjuvant chemotherapy. Then, we constructed a 10-gene signature for the prediction of clinical outcomes and verified the robustness using public cohorts (>1000 patient samples). To further investigate the clinical utilities and underlying biological mechanisms of this 10-gene panel, we plan to validate the gene signature on a 2000 Chinese cohort of the ICGC-ARGO CRC project in which the applicant participates, and integrates multi-omics data for bioinformatic analyses and functional annotation. Furthermore, we will validate the gene signature on retrospective and prospective cohorts by RT-qPCR. This study will reveal the key genes and their biological functions affecting tumor recurrence in CRC, and establish novel biomarkers for clinical practice and provide a basis for more individualized therapy of CRC patients.