BACKGROUND This study aimed to explore the heterogeneity of circRNA expression pattern via microarray, and further evaluate the potential of 10 specific circRNAs as diagnostic and prognostic biomarkers in multiple myeloma (MM). METHODS In exploration stage (stage I), circRNA expression profiles were detected by the microarray in bone marrow plasma cells from 4 MM patients and 4 healthy controls (HCs), and bioinformatic analyses were performed. In validation stage (stage II), top 10 upregulated and top 10 downregulated circRNAs identified in stage I were detected in 60 MM patients and 30 HCs for further validation; the diagnostic and prognostic values of these circRNAs in MM patients were analyzed. RESULTS In stage I, 122 upregulated and 260 downregulated circRNAs were identified in MM patients compared with HCs. GO, KEGG and pathway enrichment analyses revealed that these circRNAs were implicated in neoplastic pathways such as MAPK and VEGF signaling pathways. In stage II, circ-PTK2, circ-RNF217, circ-RERE, circ-NAGPA and circ-KCNQ5 were validated to be upregulated and circ-AFF2, circ-WWC3, circ-DNAJC5, circ-KLHL2, circ-IQGAP1 and circ-AL137655 were validated to be downregulated in MM compared with controls. Circ-PTK2 and circ-RNF217 were correlated with poor treatment response and survival, while circ-AFF2 predicted good treatment response and survival in MM patients. CONCLUSIONS This study provides valuable reference for profound understanding about circRNA expression patterns in MM, and validates that circ-PTK2, circ-RNF217 and circ-AFF2 might serve as potential prognostic biomarkers in MM.

中文翻译：

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环状RNA表达的全面分析揭示了多发性骨髓瘤中潜在的诊断和预后生物标志物。

背景技术本研究旨在通过微阵列探索circRNA表达模式的异质性，并进一步评估10种特定circRNA在多发性骨髓瘤（MM）中作为诊断和预后生物标志物的潜力。方法在探索阶段（第一阶段），通过微阵列检测了4例MM患者和4例健康对照（HCs）的骨髓浆细胞中circRNA表达谱，并进行了生物信息学分析。在验证阶段（II期），在60 MM患者和30 HCs中检测到I期中鉴定出的前10大上调和前10下调的circRNA，以进行进一步验证。分析了这些circRNA在MM患者中的诊断和预后价值。结果在第一阶段，与HCs相比，在MM患者中鉴定到122项上调的circRNA和260项下调的circRNA。走，KEGG和通路富集分析表明，这些circRNA与肿瘤通路（如MAPK和VEGF信号通路）有关。在阶段II中，验证了circ-PTK2，circ-RNF217，circ-RERE，circ-NAGPA和circ-KCNQ5被上调，并且circ-AFF2，circ-WWC3，circ-DNAJC5，circ-KLHL2，circ-IQGAP1和circ与对照相比，已确认-AL137655在MM中被下调。Circ-PTK2和circ-RNF217与不良的治疗反应和生存率相关，而circ-AFF2预测在MM患者中良好的治疗反应和生存率。结论这项研究为深入了解MM中circRNA表达模式提供了有价值的参考，并验证circ-PTK2，circ-RNF217和circ-AFF2可能是MM中潜在的预后生物标志物。