Single-Cell RNA Sequencing Unravels Distinct Tumor Microenvironment of Different Components of Lung Adenocarcinoma Featured as Mixed Ground-Glass Opacity

Abstract

Lung adenocarcinoma featured as mixed ground-glass opacity (mGGO) doubled its volume half of the time in comparison with that featured as pure ground-glass opacity (pGGO). The mechanisms underlying the heterogeneous appearance of mGGO remain elusive. In this study, we macro-dissected the solid (S) components and ground-glass (GG) components of mGGO and performed single-cell sequencing analyses of six paired components from three mGGO patients. A total of 19,391 single-cell profiles were taken into analysis, and the data of each patient were analyzed independently to obtain a common alteration. Cancer cells and macrophages were the dominant cell types in the S and GG components, respectively. Cancer cells in the S components, which showed relatively malignant phenotypes, were likely to originate from both the GG and S components and monitor the surrounding tumor microenvironment (TME) through an intricate cell interaction network. SPP1hi macrophages were enriched in the S components and showed increased activity of chemoattraction, while macrophages in the GG components displayed an active antimicrobial process with a higher stress-induced state. In addition, the CD47–SIRPA axis was demonstrated to be critical in the maintenance of the GG components. Taken together, our study unraveled the alterations of cell components and transcriptomic features between different components in mGGOs.

Promising immunotherapeutic targets in lung cancer based on single-cell RNA sequencing

“…CD47, a classic immune escape molecule, prevents immune cell maturation and the release of immune activation factors through the CD47-SIRPA axis. A scRNA-seq study further confirmed that CD47 and SIRPA were upregulated in lung cancer compared to normal lung tissue (51). Additionally, it was found that CD24 was found to be generally elevated in the epithelial cells of lung cancer.…”

“…Accumulating scRNA-seq studies have identified several representative subsets of TAMs in NSCLC, defined by the symbolic markers complement 1 q (C1Q), SPP1, triggering receptor expressed on myeloid cells-2 (TREM2), NLRP3, LYVE1 (48)(49)(50)(51)(52). Protumorigenic macrophages consist of C1Q + , SPP1 + , and TREM2 + subsets (48,49,52,53).…”

“…SPP1 + TAMs have a stronger interaction with CAFs and ECs, thereby remodeling the TME. In addition, studies have demonstrated that high SPP1 expression in macrophages promotes lung cancer invasiveness and is associated with a worse clinical outcome in multiple cancer types (48,51). TREM2 + macrophages are stably enriched in both early and late stages of lung cancer and have been defined as a pro-tumorigenic subset (48,49).…”

Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma

“…As expected, epithelial cells showed extremely high inter-tumor heterogeneity ( Figure 2 A), similar to the findings of previous studies. 13 , 14 , 15 Therefore, we attempted to identify malignant cells in the epithelial cell population through CopyKAT inference in a case-by-case manner. We obtained1355 (A304-01), 2071 (A304-02), 1542 (A304-03), and 716 (A304-04) malignant epithelial cells from the epithelial cell types ( Figure 2 B).…”

Identification of novel gene signature for lung adenocarcinoma by machine learning to predict immunotherapy and prognosis

“…From the Gene Expression Omnibus (GEO) database, scRNAseq data (GSE203360) and microarray expression profiles (GSE31210) of LUAD samples were accessed (10)(11)(12). From the Cancer Genome Atlas (TCGA) database, Bulk RNA-seq data (transcripts per million, TPM) of LUAD samples were obtained on the Sangerbox platform (13,14).…”