Lung adenocarcinoma (LUAD) generally presents as an immunosuppressive microenvironment. The characteristics of cell‐to‐cell communication in the LUAD microenvironment has been unclear. In this study, the LUAD bulk RNA‐seq data and single‐cell RNA‐seq data were retrieved from public dataset. Differential expression genes (DEGs) between LUAD tumor and adjacent non‐tumor tissues were calculated by limma algorithm, and then detected by PPI, KEGG, and GO analysis. Cell–cell interactions were explored using the single‐cell RNA‐seq data. Finally, the first 15 CytoHubba genes were used to establish related pathways and these pathways were used to characterize the immune‐related ligands and their receptors in LUAD. Our analyses showed that monocytes or macrophages interact with tissue stem cells and NK cells via SPP1 signaling pathway and tissue stem cells interact with T and B cells via CXCL signaling pathway in different states. Hub genes of SPP1 participated in SPP1 signaling pathway, which was negatively correlated with CD4+ T cell and CD8+ T cell. The expression of SPP1 in LUAD tumor tissues was negatively correlated with the prognosis. While CXCL12 participated in CXCL signaling pathway, which was positively correlated with CD4+ T cell and CD8+ T cell. The role of CXCL12 in LUAD tumor tissues exhibits an opposite effect to that of SPP1. This study reveals that tumor‐associated monocytes or macrophages may affect tumor progression. Moreover, the SPP1 and CXCL12 may be the critic genes of cell‐to‐cell communication in LUAD, and targeting these pathways may provide a new molecular mechanism for the treatment of LUAD.

中文翻译：

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单细胞和批量 RNA 测序揭示 SPP1 和 CXCL12 作为细胞间通讯标记物来预测肺腺癌的预后

肺腺癌（LUAD）通常表现为免疫抑制微环境。 LUAD 微环境中细胞间通讯的特征尚不清楚。在本研究中，从公共数据集中检索了 LUAD 批量 RNA-seq 数据和单细胞 RNA-seq 数据。通过limma算法计算LUAD肿瘤与邻近非肿瘤组织之间的差异表达基因（DEG），然后通过PPI、KEGG和GO分析进行检测。使用单细胞 RNA-seq 数据探索细胞间相互作用。最后，前 15 个 CytoHubba 基因用于建立相关通路，这些通路用于表征 LUAD 中的免疫相关配体及其受体。我们的分析表明，在不同状态下，单核细胞或巨噬细胞通过SPP1信号通路与组织干细胞和NK细胞相互作用，组织干细胞通过CXCL信号通路与T细胞和B细胞相互作用。 SPP1的Hub基因参与SPP1信号通路，与CD4+T细胞和CD8+T细胞呈负相关。 LUAD肿瘤组织中SPP1的表达与预后呈负相关。而CXCL12参与CXCL信号通路，与CD4+T细胞和CD8+T细胞呈正相关。 CXCL12在LUAD肿瘤组织中的作用表现出与SPP1相反的作用。这项研究表明，肿瘤相关的单核细胞或巨噬细胞可能会影响肿瘤的进展。此外，SPP1和CXCL12可能是LUAD中细胞间通讯的关键基因，针对这些通路可能为LUAD的治疗提供新的分子机制。