Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules.
Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules.
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以毛玻璃结节为特征的肺腺癌单细胞转录组图谱
DOI：
10.1038/s41421-020-00200-x
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发表时间：
2020
期刊：
影响因子：
33.5
通讯作者：
Tan L
中科院分区：
文献类型：
--
作者：
Lu T;Yang X;Shi Y;Zhao M;Bi G;Liang J;Chen Z;Huang Y;Jiang W;Lin Z;Xi J;Wang S;Yang Y;Zhan C;Wang Q;Tan L
作为一种早期的肺腺癌类型，磨玻璃结节（GGN）的检出率日益增加，目前在肺癌门诊患者中占多数。GGN预后良好，其特征与实性腺癌（SADC）有很大不同。我们利用单细胞RNA测序（scRNA - seq）对GGN腺癌（GGN - ADC）和SADC进行比较，以全面了解GGN。对5例肺GGN - ADC患者和5例SADC患者手术切除的肿瘤样本进行消化，制成单细胞悬液，并使用10× Genomics的scRNA - seq技术进行分析。我们获得了60459个细胞，然后将它们分为8种细胞类型，包括癌细胞、内皮细胞、成纤维细胞、T细胞、B细胞、自然杀伤细胞、肥大细胞和髓样细胞。我们对癌细胞和基质细胞进行了全面描述。我们发现，基于scRNA - seq结果分析，与细胞增殖相关的信号通路在GGN - ADC癌细胞中下调，并且基质细胞在GGN - ADC和SADC中具有不同的作用。在GGN - ADC中，血管生成的信号通路下调，成纤维细胞一些胶原蛋白表达水平较低，免疫细胞更活跃。此外，我们使用流式细胞术分离了12例GGN - ADC样本以及相同数量的SADC样本中的癌细胞和T细胞，包括CD4 + T细胞和CD8 + T细胞，并通过实时定量聚合酶链反应分析验证了关键分子的表达。通过对GGN中细胞表型的综合分析，我们对肺癌发生有了深入的了解，这将有利于肺癌的预防和治疗。
As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+T and CD8+T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy.