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中医证候分类与结直肠癌肿瘤细胞和微环境异质性的关联:单细胞RNA测序分析

Traditional chinese medicine syndromes classification associates with tumor cell and microenvironment heterogeneity in colorectal cancer: a single cell RNA sequencing analysis.

作者信息

Lu Yiyu, Zhou Chungen, Zhu Meidong, Fu Zhiliang, Shi Yong, Li Min, Wang Wenhai, Zhu Shibo, Jiang Bin, Luo Yunquan, Su Shibing

机构信息

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Department of Anorectal, Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210001, China.

出版信息

Chin Med. 2021 Dec 7;16(1):133. doi: 10.1186/s13020-021-00547-7.

Abstract

BACKGROUND

Colorectal 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.

METHODS

In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC.

RESULTS

The 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).

CONCLUSIONS

The Excess and Deficiency syndromes classification may be related to tumor heterogeneity and its microenvironment in CRC.

摘要

背景

结直肠癌(CRC)是常见的胃肠道恶性肿瘤之一,肿瘤异质性是难治性CRC的主要原因。辨证是中医个体化治疗的前提,但中医证候在CRC中缺乏客观识别。本研究旨在探讨CRC中肿瘤异质性与中医证候分类的相关性及意义。

方法

在本研究中,我们使用单细胞RNA测序(scRNA-seq)技术,研究肿瘤异质性在CRC中医证候分类中的意义。

结果

结果显示,从11例原发性CRC肿瘤中分离出的662个细胞被分为14个不同的细胞簇,每个细胞亚型及其基因具有不同的功能和信号转导途径,表明存在显著的异质性。CRC肿瘤细胞簇在实证、虚证和虚实夹杂证中的比例不同,且有各自的特征基因、基因共表达网络、基因功能诠释以及单细胞功能进化。此外,CRC实证和虚证分类中MUC2、REG4、COL1A2、POSTN、SDPR、GPX1、ELF3、KRT8、KRT18、KRT19、FN1、SERPINE1、TCF4和ZEB1基因高表达之间存在显著差异(P < 0.01)。

结论

实证和虚证分类可能与CRC中的肿瘤异质性及其微环境有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15f/8650518/7c151e00efef/13020_2021_547_Fig1_HTML.jpg

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