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.

作为肺腺癌的一种早期类型，磨玻璃结节（GGN）的检出率越来越高，目前占肺癌门诊患者的大多数。GGN预后满意，其特点与实体腺癌（SADC）有较大不同。我们使用单细胞 RNA 测序 (scRNA-seq) 将 GGN 腺癌 (GGN-ADC) 与 SADC 进行比较，以充分了解 GGN。将 5 名接受手术的肺部 GGN-ADC 患者和 5 名 SADC 患者的肿瘤样本消化成单细胞悬浮液，并使用 10× 基因组 scRNA-seq 技术进行分析。我们获得了 60,459 个细胞，然后将它们分为八种细胞类型，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、肥大细胞和骨髓细胞。我们提供了癌细胞和基质细胞的全面描述。根据scRNA-seq结果分析，我们发现GGN-ADC癌细胞中与细胞增殖相关的信号通路下调，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被下调，成纤维细胞表达低水平的某些胶原蛋白，免疫细胞被更加激活。此外，我们使用流式细胞术分离了12个GGN-ADC样本和等量SADC样本中的癌细胞和T细胞，包括CD4 ⁺ T和CD8 ⁺ T细胞，并通过定量实时验证关键分子的表达。时间聚合酶链式反应分析。通过对 GGN 中细胞表型的全面分析，我们提供了对肺癌发生的深入见解，这将有利于肺癌的预防和治疗。