CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Bioinformatics analysis of intrinsic drivers of immune dysregulation in multiple myeloma to elucidate immune phenotypes and discover prognostic gene signatures.
Bioinformatics analysis of intrinsic drivers of immune dysregulation in multiple myeloma to elucidate immune phenotypes and discover prognostic gene signatures.
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多发性骨髓瘤（MM）的进展由肿瘤微环境（TME）内的免疫失调驱动。然而，髓瘤细胞内在机制如何导致免疫功能障碍仍不明确，现有免疫疗法的疗效也有限。
我们利用859例MM患者的RNA测序数据（MMRF-CoMMpass），整合xCELL、CIBERSORT和ESTIMATE算法，解析免疫与基质动态变化。通过一致性聚类识别免疫亚型，随后进行差异基因分析和LASSO-Cox回归以构建预后模型，并在独立队列（GSE19784，N=328）中验证。免疫亚型分类：识别出两个亚组。多发性骨髓瘤相关免疫簇1（N=482）：免疫功能障碍型TME，表现为Th2细胞富集、前脂肪细胞积聚和CXCL家族受抑，并与较差生存相关（P<0.001）。多发性骨髓瘤相关免疫簇2（N=377）：免疫活化型TME，具有细胞毒性CD8+ T/NK细胞浸润，结局较好。预后基因特征：10种免疫相关基因（UBE2T、E2F2、EXO1、SH2D2A、DRP2、WNT9A、SHROOM3、TMC8、CDCA7和GPR132）可预测生存（一年AUC=0.682，超过5年AUC=0.714）。
我们构建了髓瘤细胞内在的免疫分类系统和10基因预后指数，为基于风险分层的免疫治疗提供框架。结合流式细胞术可优化MM精准治疗。
Multiple myeloma (MM) progression is driven by immune dysregulation within the tumor microenvironment (TME).
However, myeloma-intrinsic mechanisms underlying immune dysfunction remain poorly defined, and current immunotherapies show limited efficacy. Using RNA-seq data from 859 MM patients (MMRF-CoMMpass), we integrated xCELL, CIBERSORT, and ESTIMATE algorithms to deconvolute immune-stromal dynamics. Consensus clustering identified immune subtypes, followed by differential gene analysis and LASSO-Cox regression to construct a prognostic model validated in an independent cohort (GSE19784, N = 328).
Immune Subtype Classification: Two subgroups emerged: Multiple myeloma-associated immune-related cluster 1 (N = 482): Immune-dysfunctional TME with Th2 cell enrichment, preadipocyte accumulation, and CXCL family suppression, linked to poor survival (P < 0. 001).
Multiple myeloma-associated immune-related cluster 2 (N = 377): Immune-active TME with cytotoxic CD8 + T/NK cell infiltration and favorable outcomes. Prognostic Gene Signature: Ten immune-related genes (UBE2T, E2F2, EXO1, SH2D2A, DRP2, WNT9A, SHROOM3, TMC8, CDCA7, and GPR132) predicted survival (The One-year AUC = 0. 682 and The Over 5-years AUC = 0. 714).
We define a myeloma-intrinsic immune classification system and a 10-gene prognostic index, offering a framework for risk-stratified immunotherapy. Integration with flow cytometry could optimize precision treatment in MM.
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