Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions.
Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions.
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DOI：
10.1186/s13073-020-00776-9
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发表时间：
2020-09-29
期刊：
影响因子：
12.3
通讯作者：
Han H
中科院分区：
文献类型：
--
作者：
Lin W;Noel P;Borazanci EH;Lee J;Amini A;Han IW;Heo JS;Jameson GS;Fraser C;Steinbach M;Woo Y;Fong Y;Cridebring D;Von Hoff DD;Park JO;Han H
胰腺导管腺癌（PDAC）等实体瘤不仅包含肿瘤细胞，还包含肿瘤细胞不断相互作用的微环境。肿瘤微环境细胞组成的详细表征对于了解疾病和患者治疗至关重要。单细胞转录组学已用于研究不同实体瘤类型（包括PDAC）的细胞组成。然而，几乎所有这些研究都使用了原发性肿瘤组织。在这项研究中，我们采用了单细胞RNA测序技术来分析PDAC患者分离的原发性肿瘤或转移性活检组织中单个细胞的转录组。使用无监督聚类分析以及新的监督分类算法SuperCT来识别肿瘤组织中的不同细胞类型。然后在原发性肿瘤和转移性活检之间比较不同细胞类型的表达特征。使用公共数据集，细胞类型特异性标签基因的表达也与患者生存相关。我们的单细胞RNA测序分析揭示了原发性和转移性PDAC组织中不同的细胞类型，包括肿瘤细胞、内皮细胞、癌症相关成纤维细胞（CAF）和免疫细胞。癌细胞显示出高的患者间异质性，而基质细胞在患者间更同质。免疫浸润在患者之间显著不同，其中大多数免疫细胞是巨噬细胞和耗尽的淋巴细胞。我们发现肿瘤细胞组成是定义PDAC亚型的重要因素。此外，EMT+癌细胞、活化CAF和内皮细胞的细胞类型特异性标志物的表达水平与患者存活率显著相关。总之，我们的工作确定了PDAC肿瘤的细胞组成以及原发性肿瘤和转移性病变之间的显著异质性。此外，细胞组成是定义PDAC亚型的重要因素，并与患者结局显著相关。这些发现为PDAC微环境提供了有价值的见解，并可能为PDAC患者的管理提供信息。
Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues. In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets. Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival. Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1158/1078-0432.ccr-16-3122
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown JM;Recht L;Strober S
通讯作者：
Strober S
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Karaayvaz M;Cristea S;Gillespie SM;Patel AP;Mylvaganam R;Luo CC;Specht MC;Bernstein BE;Michor F;Ellisen LW
通讯作者：
Ellisen LW
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP