Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing

周细胞 免疫疗法 结直肠癌 免疫系统 肿瘤微环境 免疫检查点 癌症研究 生物标志物 癌症免疫疗法 生物 医学 癌症 免疫学 内科学 内皮干细胞 遗传学 体外
作者
Wei Chen,Weikai Wang,Zhihao Hu,Zhuoli Huang,Ye Lu,Wen-Wen Zhou,Xiaoying Liu,Xin Jin,Jianhua Yin,Guibo Li
出处
期刊:Human Molecular Genetics [Oxford University Press]
卷期号:33 (14): 1215-1228
标识
DOI:10.1093/hmg/ddae064
摘要

Abstract Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.
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