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Status |
Public on Sep 30, 2024 |
Title |
Identification of a novel signature based on immune microenvironment to predict prognosis,immunotherapeutic efficacy and immunogenicity in lung adenocarcinoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Abstract: Immunotherapy has emerged as a crucial treatment approach for lung adenocarcinoma (LUAD), yet a notable percentage of patients do not exhibit the anticipated prognosis and therapeutic response. In this study, we embarked on a comprehensive analysis of immune infiltration-related genes in LUAD by integrating transcriptome sequencing data and TCGA dataset. And an immune risk prognosis model was developed, which accurately forecasts the prognosis and predicts the immunotherapy efficacy in LUAD. Patients with LUAD were categorized into high-risk and low-risk groups based on the model's risk value. The high-risk group exhibited a poorer prognosis, higher tumor mutation burden (TMB), greater genomic heterogeneity and lower immune scores. In contrast, the low-risk group manifested characteristics conducive to immunotherapy, including a more favorable prognosis, heightened sensitivity to immunotherapy and reduced likelihood of immune escape. The robustness of the model's predictive capability was corroborated using the GEO dataset, Nomogram and an independent immunotherapy cohort. Furthermore, the model risk value was found to be significantly associated with the prognosis of LUAD patients, genomic heterogeneity, immune cell infiltration, immune regulation and immunotherapy outcomes. Additionally, we characterized the significance of the model's feature factors using single-cell clustering and pseudo-temporal analysis, revealing that the model's feature genes are predominantly located in tumor-infiltrating T cells, particularly in the exhausted and effector subtypes. TNFRSF11A emerged as a key gene in the model, promoting LUAD cell proliferation, migration, and apoptosis, and involvement in LUAD M6A methylation and PD-L1-mediated immune escape. TNFRSF11A was mainly expressed in T cell clusters and represented a potential immune system regulatory factor associated with T cell exhaustion, fostering malignant progression in LUAD cells. Our study offers new mechanistic insights and therapeutic targets for the biological behaviors and immune suppression in LUAD.
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Overall design |
Three LUAD surgical samples and Three corresponding LUAD-adjacent cancer samples were collected from hospital samples for transcriptome sequencing to identify differentially expressed lncRNAs and mRNAs in LUAD.LncRNA and mRNA profiles of 3 LUAD surgical samples and 3 corresponding LUAD paracancer samples
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Contributor(s) |
Peng P, Chen W, Li X, Pei Y, Lv J |
Citation missing |
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Submission date |
Jun 25, 2024 |
Last update date |
Sep 30, 2024 |
Contact name |
yongyan pei |
Organization name |
Guangdong Pharmaceutical University
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Department |
School of Pharmaceutical and Chemical Engineering
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Street address |
Long life water, wuguishan street, zhongshan city
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City |
zhongshan |
ZIP/Postal code |
528458 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (6)
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Relations |
BioProject |
PRJNA1128059 |
Supplementary file |
Size |
Download |
File type/resource |
GSE270711_matrix_lncRNA.count.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
GSE270711_matrix_lncRNA.fpkm.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
GSE270711_matrix_mRNA.count.txt.gz |
284.6 Kb |
(ftp)(http) |
TXT |
GSE270711_matrix_mRNA.fpkm.txt.gz |
662.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
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