Abstract
BackgroundColorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. This study is to investigate the correlation and significance of tumor heterogeneity and TCM syndromes classification in CRC.MethodsIn this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC.ResultsThe results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes in Excess and Deficiency syndrome classification in CRC (P < 0.01).ConclusionsThe Excess and Deficiency syndromes classification may be related to tumor heterogeneity and its microenvironment in CRC.
Highlights
Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC
There were the different distributions of intra-tumor cell subpopulations in different traditional Chinese medicine (TCM) syndromes including Excess syndrome (ES), Deficiency syndrome (DS) and Deficiency-Excess syndrome (DES), and the high expressions of Mucin 2 (MUC2) and regenerating islet-derived protein 4 (REG4) in DES were mainly related to brain development, cytogenesis, mitogenactivated protein kinase 1 (MAPK) and cyclic adenosine monophosphate (cAMP) signaling pathways; the high expressions of COL1A2 and POSTN genes in ES were mainly related to vascular development, skeletal muscle development, and PI3k-Akt Pathway; SDPR and glutathione peroxidase 1 (GPX1) genes were highly expressed in DS, mainly related to vomiting, platelet decomposition, and endocytosis
This study found 14 different cell subpopulations and 11 known cell lineages among 662 cells isolated from 11 primary CRC tumor tissues, including CRC cancer cells (CEACAM5 +, epithelial cell adhesion molecules (EPCAM) +, KRT 18+ and Mucin 1 (MUC1)+ cells), stem cells, immune cells, fibroblast cells (ETM like and cancer-related fibroblasts (CAFs)) and enterocyte
Summary
Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. High throughput cellular RNA sequencing technology has been widely used in transcriptome analysis to study transcriptional structure, splicing patterns, gene and transcriptional expression levels [7]. This sequencing method cannot be specific to a single cell, blurring the characteristics of different cell groups. Developed single cell RNA sequencing (scRNAseq) technology is used to measure gene expression at the single cell level in cancer research [8] It provides higher cell differential resolution than high-throughput RNA sequencing, and can analyze all cell types, gene expression profiles, characteristic genes and biological function evolution of all tumor cell types [9]. It has been applied to the study of tumor heterogeneity in some cancers, such as lung cancer [10], breast cancer [11], liver cancer [12] and CRC [13, 14]
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