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pmid:36358600

Heterogeneity and Differentiation Trajectories of Infiltrating CD8+ T Cells in Lung Adenocarcinoma.

Xiaojie Song · Guanghui Zhao · Guangqiang Wang · Haidong Gao

Cancers · 2022 doi:10.3390/cancers14215183

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Heterogeneity and Differentiation Trajectories of Infiltrating CD8+ T Cells in Lung Adenocarcinoma.
doi
10.3390/cancers14215183
pmid
36358600
authors array · 4 items
[0]
Xiaojie Song
[1]
Guanghui Zhao
[2]
Guangqiang Wang
[3]
Haidong Gao
journal
Cancers
year
2022
abstract
CD8+ T cells infiltrating the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) are critical for establishing antitumor immunity. Nevertheless, the global landscape of their numbers, functional status, and differentiation trajectories remains unclear. In the single-cell RNA-sequencing (scRNA-seq) dataset GSE131907 of LUAD, the CD8+T cells were selected for TSNE clustering, and the results showed that they could be divided into ten subsets. The cell differentiation trajectory showed the presence of abundant transition-state CD8+ T cells during the differentiation of naive-like CD8+ T cells into cytotoxic CD8+ T cells and exhausted CD8+ T cells. The differentially expressed marker genes among subsets were used to construct the gene signature matrix, and the proportion of each subset was identified and calculated in The Cancer Genome Atlas (TCGA) samples. Survival analysis showed that the higher the proportion of the exhausted CD8+ T lymphocyte (ETL) subset, the shorter the overall survival (OS) time of LUAD patients (p = 0.0098). A total of 61 genes were obtained by intersecting the differentially expressed genes (DEGs) of the ETL subset, and the DEGs of the TCGA samples were divided into a high and a low group according to the proportion of the ETL subset. Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes. Our study further deepens the understanding of the heterogeneity and functional exhaustion of infiltrating CD8+ T cells in LUAD. The screened prognostic marker genes provide potential targets for targeted therapy and immunotherapy in LUAD patients.
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Survival analysis was performed on candidate hub genes using the R ‘survival’ package, and the genes with a significant effect on prognosis were selected as hub genes.
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The GSE131907 dataset is available from the GEO database. TCGA-LUAD sample data can be obtained from the TCGA database. Additional information is available from articles or supplementary files. The codes used for analysis have uploaded to the GitHub website. Please access it from the following link: https://github.com/qilugaohaidong/R_script, accessed on 10 October 2022.
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The GSE131907 dataset is available from the GEO database. TCGA-LUAD sample data can be obtained from the TCGA database. Additional information is available from articles or supplementary files. The codes used for analysis have uploaded to the GitHub website. Please access it from the following link: https://github.com/qilugaohaidong/R_script, accessed on 10 October 2022.
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Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes.
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Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes.
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Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes.
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Survival analysis was performed on candidate hub genes using the R ‘survival’ package, and the genes with a significant effect on prognosis were selected as hub genes.
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In the single-cell RNA-sequencing (scRNA-seq) dataset GSE131907 of LUAD, the CD8+T cells were selected for TSNE clustering, and the results showed that they could be divided into ten subsets. The cell differentiation trajectory showed the presence of abundant transition-state CD8+ T cells during the differentiation of naive-like CD8+ T cells into cytotoxic CD8+ T cells and exhausted CD8+ T cells. The differentially expressed marker genes among subsets were used to construct the gene signature matrix, and the proportion of each subset was identified and calculated in The Cancer Genome Atlas (TCGA) samples. Survival analysis showed that the higher the proportion of the exhausted CD8+ T lymphocyte (ETL) subset, the shorter the overall survival (OS) time of LUAD patients (p = 0.0098). A total of 61 genes were obtained by intersecting the differentially expressed genes (DEGs) of the ETL subset, and the DEGs of the TCGA samples were divided into a high and a low group according to the proportion of the ETL subset. Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes. Our study further deepens the understanding of the heterogeneity and functional exhaustion of infiltrating CD8+ T cells in LUAD. 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