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pmid:38681062
Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma.
Ling Lv · Xin Zhang · Yajun Liu · Xutong Zhu · Ruihan Pan · Lifa Huang
Pharmacogenomics and personalized medicine · 2024 doi:10.2147/PGPM.S442000
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Experiment
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Complete file
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However, the association between LLPS-associated genes and glioma remains underexplored.\nPatients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR.\nResults: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells.\nConclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.", "claims": [{"id": "claim-method", "statement": "The glmnet package in R version 4.2.2 was employed for lasso Cox multivariate regression, with the Log rank test for correction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38681062", "locator": "sections[8] \"Prognostic Model Construction and Validation\" paragraph 2", "quote": "The glmnet package in R version 4.2.2 was employed for lasso Cox multivariate regression, with the Log rank test for correction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author, [LH], on special request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38681062", "locator": "sections[21] \"Data Sharing Statement\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author, [LH], on special request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A tri-gene prognostic signature comprising TAGLN2, NTNG2, and IGF2BP2 was derived, and the model showed significant survival differences between high- and low-risk groups with AUC values of 0.842, 0.859, and 0.757 for 1-, 3-, and 5-year survival in the training set and 0.932, 0.843, and 0.684 in the validation set.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "The KM showed significant survival differences between high and low-risk groups in both training and validation sets (Log rank test, p < 0.0001)."}, "evidence": [{"asset": "source:pmid:38681062", "locator": "sections[16] \"Construction and Performance Evaluation of the Prognostic Model\" paragraph 2", "quote": "Through the lasso Cox regression, we discerned a composite prognostic signature comprising three genes (TAGLN2, NTNG2, and IGF2BP2) from the 312 survival-correlated genes (Figure 4A)."}, {"asset": "source:pmid:38681062", "locator": "sections[16] \"Construction and Performance Evaluation of the Prognostic Model\" paragraph 4", "quote": "The KM showed significant survival differences between high and low-risk groups in both training and validation sets (Log rank test, p < 0.0001)."}, {"asset": "source:pmid:38681062", "locator": "sections[16] \"Construction and Performance Evaluation of the Prognostic Model\" paragraph 4", "quote": "ROC analysis showed that the prognostic model had good prognostic properties for 1-year (AUC: 0.842), 3-year (AUC: 0.859), and 5-year (AUC: 0.757) survival in the training set (Figure 4B)."}, {"asset": "source:pmid:38681062", "locator": "sections[16] \"Construction and Performance Evaluation of the Prognostic Model\" paragraph 4", "quote": "The good prognostic properties also presented for 1-year (AUC: 0.932), 3-year (AUC: 0.843), and 5-year (AUC: 0.684) survival in the validation set (Figure 4C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A tri-gene prognostic signature comprising TAGLN2, NTNG2, and IGF2BP2 was derived, and the model showed significant survival differences between high- and low-risk groups with AUC values of 0.842, 0.859, and 0.757 for 1-, 3-, and 5-year survival in the training set and 0.932, 0.843, and 0.684 in the validation set.", "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:38681062"], "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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