GSE110009
Single cell transcriptome landscape of primary and metastatic tumor in colon cancer
Colorectal Cancer ranks as the second-leading cause of cancer-related death worldwide. Recent progress in colon cancer research has vastly expanded our understanding of colon cancer on the cellular and molecular levels and have improved the survival of CRC patients considerably. However, most of these genomic and gene expression profiling were usually characterized by bulk tumor tissue. In order to further understanding colon cancer, knowledge at the single cell level is urgently needed and expected to have clinical utility in cancer treatment. Single-cell transcriptome profiling of tumor tissues allows the characterization of heterogeneous tumor cells with neighbor microenvironment cell components and investigation of underlying mechanism of tumorigenesis and metastasis. Here, we adopt single cell RNA-Seq to colon cancer and analyze 3,585 cells from 6 patients with matching adjacent normal tissues, primary tumors and metastatic tumors. Most of tumor cells exhibit copy number variations and diverse CNV patterns existed. Novel markers have been identified to distinguish tumour from normal cells and even work for cancer cells that did not have CNVs. Compared with adjacent normal tissue, the number of stem cell and Paneth cell increased and the surrounding cancer-association cells like immune cells in microenvironment increased in tumour region. Moreover, the interaction of tumour cell and microenvironment cells have been elaborated. Our results demonstrate that colon cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by tumor cells and cancer associated cells in the surrounding microenvironment. Overall design: Single cell transcriptome profiles of six colon cancer patients were generated by next-generation sequencing using Illumina HiSeq 4000. In order to confirm the copy number variants inferred by single cell RNA-seq data, bulk whole genome sequencing were performed on normal tissue and tumor regions.