Title PNOC Expressed by B Cells in Cholangiocarcinoma Was Survival Related and LAIR2 Could Be a T Cell Exhaustion Biomarker in Tumor Microenvironment: Characterization of Immune Microenvironment Combining Single-Cell and Bulk Sequencing Technology
Authors Chen, Zheng
Yu, Mincheng
Yan, Jiuliang
Guo, Lei
Zhang, Bo
Liu, Shuang
Lei, Jin
Zhang, Wentao
Zhou, Binghai
Gao, Jie
Yang, Zhangfu
Li, Xiaoqiang
Zhou, Jian
Fan, Jia
Ye, Qinghai
Li, Hui
Xu, Yongfeng
Xiao, Yongsheng
Affiliation Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Shanghai, Peoples R China
Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China
Fudan Univ, Zhongshan Hosp, Neurosurg Dept, Shanghai, Peoples R China
Nanchang Univ, Dept Hepatobiliary & Pancreat Surg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China
Peking Univ, Dept Thorac Surg, Shenzhen Hosp, Shenzhen, Peoples R China
Issue Date 24-Mar-2021
Publisher FRONTIERS IN IMMUNOLOGY
Abstract Background Cholangiocarcinoma was a highly malignant liver cancer with poor prognosis, and immune infiltration status was considered an important factor in response to immunotherapy. In this investigation, we tried to locate immune infiltration related genes of cholangiocarcinoma through combination of bulk-sequencing and single-cell sequencing technology. Methods Single sample gene set enrichment analysis was used to annotate immune infiltration status in datasets of TCGA CHOL, GSE32225, and GSE26566. Differentially expressed genes between high- and low-infiltrated groups in TCGA dataset were yielded and further compressed in other two datasets through backward stepwise regression in R environment. Single-cell sequencing data of GSE138709 was loaded by Seurat software and was used to examined the expression of infiltration-related gene set. Pathway changes in malignant cell populations were analyzed through scTPA web tool. Results There were 43 genes differentially expressed between high- and low-immune infiltrated patients, and after further compression, PNOC and LAIR2 were significantly correlated with high immune infiltration status in cholangiocarcinoma. Through analysis of single-cell sequencing data, PNOC was mainly expressed by infiltrated B cells in tumor microenvironment, while LAIR2 was expressed by Treg cells and partial GZMB+ CD8 T cells, which were survival related and increased in tumor tissues. High B cell infiltration levels were related to better overall survival. Also, malignant cell populations demonstrated functionally different roles in tumor progression. Conclusion PNOC and LAIR2 were biomarkers for immune infiltration evaluation in cholangiocarcinoma. PNOC, expressed by B cells, could predict better survival of patients, while LAIR2 was a potential marker for exhaustive T cell populations, correlating with worse survival of patients.
URI http://hdl.handle.net/20.500.11897/611532
ISSN 1664-3224
DOI 10.3389/fimmu.2021.647209
Indexed SCI(E)
Appears in Collections: 深圳医院

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