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pmid:39397989
Establish a novel immune-related gene prognostic risk index (IRGPRI) associated with CD8+ cytotoxic T lymphocytes in non-small-cell lung cancer (NSCLC).
Shenjing Cui · Yikun Yang · Shuang Lou · Rong Huang · Jing Wang · Zhongbiao Chen · Jingjing Xie
Heliyon · 2024 doi:10.1016/j.heliyon.2024.e38324
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Experiment
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Complete file
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The construction of IRGPRI was accomplished by employing LASSO Cox regression analysis. We conducted a comparative analysis on clinical characteristics and molecular features, such as pathway enrichment and gene mutation, among the distinct subgroups of IRGPRI. Furthermore, we explored the correlation between immunological characteristics and IRGPRI subgroups to comprehensively assess the effectiveness of ICIs in NSCLC patients.\nResults: A total of 109 genes were identified by intersecting immune-related genes with DEGs obtained from single-cell RNA sequencing data (GSE131907), specifically comparing CTLs to other cell types. From these, we selected 7 prognosis-related genes, namely TRBC1, HLA-DMA, CTSH, RAC1, CTSL, ANXA2, and CEBPB. These genes were used to construct the IRGPRI. The prognosis of patients diagnosed with NSCLC was found to be significantly better in the low-risk group compared to the high-risk group, as demonstrated by Kaplan-Meier (K-M) survival analysis. This observation was further confirmed through the utilization of data from the GEO cohort. The low-risk group demonstrated an increase in pathways linked with immune response, whereas the high-risk group exhibited a higher prevalence of pathways related to cancer. Furthermore, it was noted in the TCGA cohort that there existed a significant rise in the mutation frequency of every gene within the high-risk group as opposed to the low-risk group. Missense variation emerged as the most prevalent form of mutation. According to the analysis of immune cell infiltration and function, the comprehensive findings suggest that the group with a low risk is characterized by an increased presence of plasma cells, CTLs, T cells follicular helper, Tregs, and Dendritic cell resting. Additionally, they exhibit a higher score in terms of immune function for B cells, CD8+ T cells, checkpoint activity, T cell inhibition and stimulation. Moreover, this low-risk group demonstrates greater efficacy when treated with ICIs therapy compared to the high-risk group.\nConclusions: Our research effectively developed and verified a unique IRGPRI, showcasing its association with immune-related characteristics. As a result, the potential of IRGPRI as a valuable biomarker for predicting prognosis and evaluating the effectiveness of ICIs treatment in cancer is evident.", "claims": [{"id": "claim-method", "statement": "The construction of IRGPRI was accomplished by employing LASSO Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39397989", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The construction of IRGPRI was accomplished by employing LASSO Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The present study utilized publicly available datasets, which can be accessed through the following sources: TCGA (https://portal.gdc.cancer.gov), GEO (https://www.ncbi.nlm.nih.gov/geo/), ImmPort (https://www.immport.org/shared/home), InnateDB (https://www.innateDBdb.com), and TISCH 2 (http://tisch.comp-genomics.org).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39397989", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The present study utilized publicly available datasets, which can be accessed through the following sources: TCGA (https://portal.gdc.cancer.gov), GEO (https://www.ncbi.nlm.nih.gov/geo/), ImmPort (https://www.immport.org/shared/home), InnateDB (https://www.innateDBdb.com), and TISCH 2 (http://tisch.comp-genomics.org)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The prognosis of patients diagnosed with NSCLC was found to be significantly better in the low-risk group compared to the high-risk group, as demonstrated by Kaplan-Meier (K-M) survival analysis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39397989", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The prognosis of patients diagnosed with NSCLC was found to be significantly better in the low-risk group compared to the high-risk group, as demonstrated by Kaplan-Meier (K-M) survival analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The prognosis of patients diagnosed with NSCLC was found to be significantly better in the low-risk group compared to the high-risk group, as demonstrated by Kaplan-Meier (K-M) survival analysis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39397989"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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