Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma
Abstract Background Tumor-associated macrophages (TAMs) play pivotal roles in innate immunity and contribute to the advancement of lung cancer. We aimed to identify novel TAM-related biomarkers and significance of macrophage infiltration in lung adenocarcinoma (LUAD) through an integrative analysis...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-03-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-01834-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850028015371681792 |
|---|---|
| author | Xiaotong Guo Youjun Deng Wenjun Jiang Heng Li Yisheng Luo Huachuan Zhang Hao Wu |
| author_facet | Xiaotong Guo Youjun Deng Wenjun Jiang Heng Li Yisheng Luo Huachuan Zhang Hao Wu |
| author_sort | Xiaotong Guo |
| collection | DOAJ |
| description | Abstract Background Tumor-associated macrophages (TAMs) play pivotal roles in innate immunity and contribute to the advancement of lung cancer. We aimed to identify novel TAM-related biomarkers and significance of macrophage infiltration in lung adenocarcinoma (LUAD) through an integrative analysis of single-cell RNA-sequencing (scRNA-seq) data. To describe the cell atlas and construct a novel prognostic signature in LUAD. Methods The gene signature linked to TAMs was identified utilizing Scanpy from the scRNA-seq dataset GSE131907. Subsequent analysis involved evaluating the expression levels of these genes, their potential molecular mechanisms, and prognostic significance in LUAD using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We also constructed a risk score models through LASSO Cox regression for these genes. The underlying mechanism was further elucidated through the application of GSEA, ESTIMATE, TIDE, and other bioinformatic algorithms. Results Single-cell atlas was described by analyze 29 scRNA-seq samples from 19 LUAD patients. The TAMs-related gene signature (TGS) was identified as an independent prognostic factor by LASSO Cox regression analysis using differential expression genes (DEGs) derived from pro- and anti-inflammatory macrophage cells. Risk score model including nine TAMs-related genes (FOSL1, ZNF697, ADM, UBE2S, TICAM1, S100P, BIRC3, TLE1, and DEFB1) were obtained for prognosis construction. Moreover, the risk model underwent additional validation in four external GEO cohorts: GSE31210, GSE72094, GSE26939, and GSE30219. Interestingly, TGS-high tumors revealed enrichments in TGF-β signaling and hypoxia pathways, which shown low immune infiltration and immunosuppression by ESTIMATE and TIDE algorithm. The TGS-high risk group exhibited lower richness and diversity in the T-cell receptor (TCR) repertoire. Conclusion This study introduces a novel TGS score developed through LASSO Cox regression analysis, utilizing DEGs in pro- and anti-inflammatory macrophage cells. High TGS tumors exhibited enrichment in TGF-β signaling and hypoxia pathways, suggesting their potential utility in predicting prognosis and immune responses in patients with LUAD. These results offer promising implications for the development of therapeutic strategies for LUAD. |
| format | Article |
| id | doaj-art-9627b9de02a4423bbb90a79c310aa77f |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-9627b9de02a4423bbb90a79c310aa77f2025-08-20T02:59:57ZengSpringerDiscover Oncology2730-60112025-03-0116111510.1007/s12672-025-01834-7Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinomaXiaotong Guo0Youjun Deng1Wenjun Jiang2Heng Li3Yisheng Luo4Huachuan Zhang5Hao Wu6Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center Shenzhen Cancer HospitalDepartment of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center Shenzhen Cancer HospitalRadiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer HospitalDepartment of Thoracic Surgery, Yunnan Hospital of OncologyDepartment of Thoracic Surgery, Shenzhen Second People’s HospitalDepartment of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment of Thoracic Surgery, Shenzhen Second People’s HospitalAbstract Background Tumor-associated macrophages (TAMs) play pivotal roles in innate immunity and contribute to the advancement of lung cancer. We aimed to identify novel TAM-related biomarkers and significance of macrophage infiltration in lung adenocarcinoma (LUAD) through an integrative analysis of single-cell RNA-sequencing (scRNA-seq) data. To describe the cell atlas and construct a novel prognostic signature in LUAD. Methods The gene signature linked to TAMs was identified utilizing Scanpy from the scRNA-seq dataset GSE131907. Subsequent analysis involved evaluating the expression levels of these genes, their potential molecular mechanisms, and prognostic significance in LUAD using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We also constructed a risk score models through LASSO Cox regression for these genes. The underlying mechanism was further elucidated through the application of GSEA, ESTIMATE, TIDE, and other bioinformatic algorithms. Results Single-cell atlas was described by analyze 29 scRNA-seq samples from 19 LUAD patients. The TAMs-related gene signature (TGS) was identified as an independent prognostic factor by LASSO Cox regression analysis using differential expression genes (DEGs) derived from pro- and anti-inflammatory macrophage cells. Risk score model including nine TAMs-related genes (FOSL1, ZNF697, ADM, UBE2S, TICAM1, S100P, BIRC3, TLE1, and DEFB1) were obtained for prognosis construction. Moreover, the risk model underwent additional validation in four external GEO cohorts: GSE31210, GSE72094, GSE26939, and GSE30219. Interestingly, TGS-high tumors revealed enrichments in TGF-β signaling and hypoxia pathways, which shown low immune infiltration and immunosuppression by ESTIMATE and TIDE algorithm. The TGS-high risk group exhibited lower richness and diversity in the T-cell receptor (TCR) repertoire. Conclusion This study introduces a novel TGS score developed through LASSO Cox regression analysis, utilizing DEGs in pro- and anti-inflammatory macrophage cells. High TGS tumors exhibited enrichment in TGF-β signaling and hypoxia pathways, suggesting their potential utility in predicting prognosis and immune responses in patients with LUAD. These results offer promising implications for the development of therapeutic strategies for LUAD.https://doi.org/10.1007/s12672-025-01834-7Single-cell RNA-sequencingTumor-associated macrophages (TAMs)Lung adenocarcinoma (LUAD)PrognosisTGF-β signalingImmune infiltration |
| spellingShingle | Xiaotong Guo Youjun Deng Wenjun Jiang Heng Li Yisheng Luo Huachuan Zhang Hao Wu Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma Discover Oncology Single-cell RNA-sequencing Tumor-associated macrophages (TAMs) Lung adenocarcinoma (LUAD) Prognosis TGF-β signaling Immune infiltration |
| title | Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| title_full | Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| title_fullStr | Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| title_full_unstemmed | Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| title_short | Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| title_sort | single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma |
| topic | Single-cell RNA-sequencing Tumor-associated macrophages (TAMs) Lung adenocarcinoma (LUAD) Prognosis TGF-β signaling Immune infiltration |
| url | https://doi.org/10.1007/s12672-025-01834-7 |
| work_keys_str_mv | AT xiaotongguo singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT youjundeng singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT wenjunjiang singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT hengli singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT yishengluo singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT huachuanzhang singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma AT haowu singlecelltranscriptomicanalysisrevealstumorimmuneinfiltrationbymacrophagecellsgenesignatureinlungadenocarcinoma |