Table_1_Integrated Transcriptomic Analysis Reveals a Distinctive Role of YAP1 in Extramedullary Invasion and Therapeutic Sensitivity of Multiple Myeloma.xlsx

Multiple myeloma (MM) is the second most common hematologic malignancy. There are no standard therapeutic guidelines for extramedullary invasion (EM). We performed a retrospective integrated transcriptomic analysis based on GEO, TCGA, and Oncomine datasets with a total of over 2,500 cases enrolled. GSVA analysis was performed on GSE24080. The external validation cohorts include GSE9782, GSE2658, MMRF-COMPASS, and Oncomine. The data of MGUS to relapsed MM were acquired from GSE6477, GSE5900, and Oncomine. The data of EM were acquired from GSE39683 and GSE66291. Single-cell level transcriptome data of MM and EM were acquired from GSE106218. GSVA analysis revealed that 559 cases could be divided into 2 groups based on the expression of oncogenic pathways with prognostic significances. Group 1 with a specific phenotype of YAP1-MYC+ exhibited an unpromising prognosis. The univariate analysis revealed YAP1 as a tumor suppressor in MM. The activity of DNA repair, glycolysis, and oxidative phosphorylation was significantly higher in YAP1-MYC+ MM, which is in concordance with EM myeloma cells based on single-cell analysis. Furthermore, we discovered that YAP1-MYC+ MM patients exhibited an improved response for IMiD treatment. Collectively, YAP1-MYC+MM patients might suffer a worse prognosis and stronger propensity for EM progression.

多发性骨髓瘤（MM）乃第二常见之血液系统恶性肿瘤。针对骨髓外侵袭（EM）尚无标准化治疗方案。本研究基于GEO、TCGA和Oncomine数据集，对超过2500例病例进行回顾性整合转录组学分析。对GSE24080数据集执行GSVA分析。外部验证队列包括GSE9782、GSE2658、MMRF-COMPASS和Oncomine。MGUS至复发性MM的数据来源于GSE6477、GSE5900和Oncomine。EM数据来源于GSE39683和GSE66291。MM和EM的单细胞水平转录组数据来源于GSE106218。GSVA分析显示，基于具有预后意义的致癌通路表达，559个病例可分为两组。第一组具有YAP1-MYC+的特定表型，预后不佳。单变量分析表明YAP1在MM中为抑癌基因。YAP1-MYC+ MM中DNA修复、糖酵解和氧化磷酸化活性显著升高，与基于单细胞分析结果的EM骨髓瘤细胞相一致。此外，我们还发现YAP1-MYC+ MM患者对IMiD治疗的反应有所改善。综上所述，YAP1-MYC+ MM患者可能面临更差的预后和更强的EM进展倾向。