Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.
多发性骨髓瘤（MM）是一种异质性浆细胞恶性肿瘤，现有的预后模型在捕捉结局变异性的全谱方面存在局限性。利用单细胞RNA测序数据，我们开发了一种新的浆细胞基因特征。我们使用来自五项独立骨髓瘤研究的数据，包括2115个样本（1978例MM、65例意义未明的单克隆丙种球蛋白病、35例冒烟型MM和37例健康对照），评估并验证了所得浆细胞恶性肿瘤（PBM）评分与疾病状态、进展和临床结局的关联。总体而言，较高的PBM评分与浆细胞疾病谱系中更晚期的阶段（所有p < 0.05）以及MM患者较短的总生存期（风险比HR = 1.72；p < 0.001）显著相关。值得注意的是，PBM评分的预后效应独立于国际分期系统（ISS）和修订的国际分期系统（R-ISS）。下游分析进一步将较高的PBM评分与细胞遗传学异常、TP53突变以及骨髓瘤肿瘤免疫微环境的组成变化联系起来。我们的整合分析表明，PBM评分可能为完善风险分层和指导MM治疗策略的决策提供机会。
肿瘤(癌症)患者之家