中文摘要
异质性是恶性肿瘤的重要特性。深入研究肿瘤细胞的发生、发展、演进以及逃避免疫监视,甚至凭借直接浸润或通过循环系统向远处转移的微进化过程对我们了解这种恶性疾病具有非常重要的意义。然而至今在单细胞层面,这种微进化过程仍然缺乏深入研究。本研究分别对同一病人来源的结肠癌原发灶、肝转移灶、淋巴结转移癌细胞、循环肿瘤细胞进行单细胞分选、捕获,并开展单细胞RNA、DNA二代测序研究。通过生物信息学方法对大规模单细胞测序数据进行分析和进化建模,了解结肠癌发生、演进、和转移过程中的微进化分子机制。以期对肿瘤通过微进化实现治疗抵抗及免疫逃逸的机制进行更深入的剖析。
英文摘要
Heterogeneity is an important property of tumor cells. The microevolution process of tumor cells during the period of tumorigenesis, tumor progress, and tumor metastasis plays a key role in understanding this disease. However, currently a detailed study of microevolution of tumor cells at single-cell level is still lacking. In the proposed study, we collect samples from colon cancer patients at primary location, liver metastatic location, metastatic lymph node, and blood stream circulation tumor cells. We use the latest single cell DNA and RNA sequencing technology to sequence a population of cells at each sample. Then, we develop bioinformatics methods to analyze the large data sets and build evolution models to study the molecular microevolution process of colon tumor progress.
