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.
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.
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胆管癌中 B 细胞表达的 PNOC 与生存相关，LAIR2 可能是肿瘤微环境中 T 细胞耗竭的生物标志物：结合单细胞和批量测序技术的免疫微环境表征
DOI：
10.3389/fimmu.2021.647209
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发表时间：
2021
影响因子：
7.3
通讯作者：
Xiao Y
中科院分区：
文献类型：
--
作者：
Chen Z;Yu M;Yan J;Guo L;Zhang B;Liu S;Lei J;Zhang W;Zhou B;Gao J;Yang Z;Li X;Zhou J;Fan J;Ye Q;Li H;Xu Y;Xiao Y
胆管癌是一种预后不良的高度恶性肝癌，免疫浸润状况被认为是影响免疫治疗效果的重要因素。在本研究中，我们试图通过结合批量测序和单细胞测序技术来定位胆管癌免疫浸润相关基因。方法采用单样本基因集富集分析方法，对TCGA CHOL、GSE32225和GSE26566数据集的免疫浸润状态进行标注。在R环境下通过反向逐步回归得到TCGA数据集中高浸润组和低浸润组之间的差异表达基因，并在其他两个数据集中进一步压缩。通过Seurat软件加载GSE138709的单细胞测序数据，检测浸润相关基因集的表达。通过scTPA网络工具分析恶性细胞群的通路变化。结果高、低免疫浸润患者有43个基因差异表达，进一步压缩后发现PNOC和LAIR2与胆管癌高免疫浸润状态显著相关。通过单细胞测序数据分析，PNOC在肿瘤微环境中主要由浸润的B细胞表达，LAIR2在肿瘤组织中由Treg细胞和部分GZMB+ CD8 T细胞表达，与肿瘤存活相关，且在肿瘤组织中表达增多。高B细胞浸润水平与较好的总生存率相关。此外，恶性细胞群在肿瘤进展中表现出不同的功能作用。结论PNOC和LAIR2是评价胆管癌免疫浸润的生物标志物。由B细胞表达的PNOC可以预测患者更好的生存，而LAIR2是穷竭T细胞群的潜在标记物，与患者更差的生存相关。
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.
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影响因子：
3.7
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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Calderaro J
DOI：
10.1016/j.ejca.2017.09.005
发表时间：
2017-11
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
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