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Construction and validation of a risk scoring model for diffuse large B-cell lymphoma based on endoplasmic reticulum stress-related and immune-related genes

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摘要 Purpose The study aimed to integrate genes associated with endoplasmic reticulum stress and immune responses to create a validated prognostic model for DLBCL.The research identified novel prognostic model and provided insights for developing innovative immunotherapies and anti-tumor strategies for DLBCL.Methods The study utilized GEO data to identify prognostically significant genes via Cox regression and developed a Lasso-Cox-based prognostic model.Patients were divided into high-and low-risk groups,with survival differences analyzed using Kaplan-Meier.Independent prognostic factors were identified through univariate and multivariate Cox analyses,and model accuracy was evaluated with ROC curves.A nomogram was developed utilizing the"rms"R package.Immune infiltration and microenvironment differences were assessed with CIBERSORT,ssGSEA,and ESTIMATE.Results Our study developed a prognostic model using 10 genes that effectively categorized DLBCL patients into high-and low-risk cohorts,and the high-risk group revealed poorer outcomes(P<0.001).Predictive AUCs for survival at 1,3,and 5 years were 0.667,0.727,and 0.729.Significant differences were observed in DLBCL samples stratified by stage,ECOG score,and LDH level.In patients aged<65 years,with<2 extranodal sites,ECOG<2,GCB or non-GCB subtype,normal LDH levels,or stage III-IV,high-risk patients had worse survival outcomes(P<0.05).The risk score model outperformed other clinicopathological factors in predicting OS(P<0.0001,HR=3.373)and was an independent risk factor alongside age,ECOG score,and COO classification.Significant differences were observed in immune cell infiltration,immune functions,checkpoints,and tumor priming between risk groups.Conclusions In this study,we developed a risk scoring model based on endoplasmic reticulum stress and immunity to stratify DLBCL patients into low-and high-risk groups.Integrating this prognostic model with clinical parameters,we constructed a comprehensive nomogram.The identification of 10 key genes offers valuable prognostic targets for treatment and provides new perspectives for advancing therapeutic strategies in DLBCL.
出处 《Holistic Integrative Oncology》 2025年第1期553-569,共17页 整合肿瘤学(英文)
基金 supported by grants from the Distinguished Taishan Scholars in Climbing Plan(tspd20210321) the Distinguished Taishan Scholars Plan(tstp20230653)the National Natural Science Foundation of China(82170182,82470153,82470180) the horizontal subject of Shandong University(6010123101) the Young Elite sponsorship Program of Shandong Provincial Medical Association(2023-LC-0336) the Innovative Team of Outstanding Youth in Colleges and Universities of Shandong Province(2023KJ022).
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