Dataset Information

T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma.

ABSTRACT:

Background

Although immune checkpoint inhibitors (ICI) are a promising therapeutic strategy for lung adenocarcinoma (LUAD), individual subgroups that might benefit from them are yet to be identified. As T cell-mediated tumor killing (TTK) is an underlying mechanism of ICI, we identified subtypes based on genes associated with TTK sensitivity and assessed their predictive significance for LUAD immunotherapies.

Methods

Using high-throughput screening techniques, genes regulating the sensitivity of T cell-mediated tumor killing (GSTTK) with differential expression and associations with prognosis were discovered in LUAD. Furthermore, patients with LUAD were divided into subgroups using unsupervised clustering based on GSTTK. Significant differences were observed in the tumor immune microenvironment (TIME), genetic mutation and immunotherapy response across subgroups. Finally, the prognostic significance of a scoring algorithm based on GSTTK was assessed.

Results

A total of 6 out of 641 GSTTK exhibited differential expression in LUAD and were associated with prognosis. Patients were grouped into two categories based on the expression of the six GSTTK, which represented different TTK immune microenvironments in LUAD. Immune cell infiltration, survival difference, somatic mutation, functional enrichment and immunotherapy responses also varied between the two categories. Additionally, a scoring algorithm accurately distinguished overall survival rates across populations.

Conclusions

TTK had a crucial influence on the development of the varying TIME. Evaluation of the varied TTK modes of different tumors enhanced our understanding of TIME characteristics, wherein the changes in T cell activity in LUAD are reflected. Thus, this study guides the development of more effective therapeutic methods.

SUBMITTER: Ding P

PROVIDER: S-EPMC9739876 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma.

Ding Peng P Liu Lichao L Bin Yawen Y Huang Yu Y Chen Lingjuan L Wen Lu L Zhang Ruiguang R Tong Fan F Dong Xiaorong X

Journal of clinical medicine 20221205 23

<h4>Background</h4>Although immune checkpoint inhibitors (ICI) are a promising therapeutic strategy for lung adenocarcinoma (LUAD), individual subgroups that might benefit from them are yet to be identified. As T cell-mediated tumor killing (TTK) is an underlying mechanism of ICI, we identified subtypes based on genes associated with TTK sensitivity and assessed their predictive significance for LUAD immunotherapies.<h4>Methods</h4>Using high-throughput screening techniques, genes regulating the ...[more]

PMID: 36498802

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Project description:BackgroundPyroptosis is a newly found form of programmed cell death, accompanied by inflammatory response as well as immune response. Here, the specific function and prognosis predictive of pyroptosis-related genes (PRGs) were systematically explored in lung adenocarcinoma (LUAD).MethodsThe gene expression data and corresponding clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the expression level of PRGs was identified between normal and tumor tissues. Furthermore, univariate Cox proportional hazards regression was conducted to filter the PRGs related to overall survival, and least absolute shrinkage and selection operator (LASSO) regression was subsequent employed to establish the PRGs risk model. Besides, the correlation of risk score with patients' clinical features, tumor mutational burden (TMB) as well as tumor microenvironment (TME) was also investigated.ResultsA total of 5 PRGs (NLRC4, NLRP1, NLRP3, NOD1, PLCG1, and BAK1) was used to establish the risk prognostic model. According the median value of risk score, all the patients were classified into low- and high-risk score group. Kaplan-Meier analysis indicted that the LUAD patients in low-risk group exhibited a better survival outcome compared the patients in high-risk group (P<0.001). After adjusting for age, gender, and clinical stage, the risk score was also considered as and independent risk factor affecting the overall survival of LUAD patients (HR =2.949, 95% CI: 1.762-4.937). Moreover, low-risk score group exhibited a higher Immune score and lower Tumor purity compared with high-risk score group. ssGSEA results proved that the enrichment scores of most immune cells and immune related signal pathway in low-risk score group was significant higher than that in high-risk score group. In addition, the PRGs risk score was also positive correlated with TMB in LUAD tissues.ConclusionsIn this study, a novel prognostic model based on PRGs was constructed and used to predict the survival outcome of LUAD patients. In addition, the PRGs risk signature was also associated with TMB and anti-tumor immune environment. The induction of pyroptosis inside tumors might be considered a potential strategy in cancer treatments.

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Dataset Information

T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma.

Similar Datasets

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