Department of Scientific Research, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211024551. doi: 10.1177/15330338211024551.
Multiple myeloma (MM) is one of the main blood disorders threatening human health today. This study aimed to examine the expression of BCL-2/adenovirus E1B 19 kDa-interacting protein 3-like (BNIP3L) in patients with MM and explore its mechanisms in silico. Bone marrow samples (n = 36 from patients with MM and n = 12 from healthy donors) were used to conduct BNIP3L expression analysis using immunohistochemistry. Microarray or RNA sequencing data from the Sequence Read Archive, Gene Expression Omnibus, and ArrayExpress databases were used to appraise BNIP3L expression and its prognostic role in patients with MM. The co-expressed genes of BNIP3L were identified for enrichment and protein-protein interaction (PPI) analyses to determine the associated signaling pathways. Immunohistochemistry indicated that BNIP3L expression in bone marrow of patients with MM was significantly lower than that in bone marrow of healthy donors. BNIP3L mRNA expression was also significantly lower in patients with MM than in healthy donors. The overall standard mean difference (SMD) for downregulation of BNIP3L was -0.62 [-1.17, -0.06], and the area under the curve was 0.81 [0.78, 0.85] based on a total of 694 MM cases. The overall survival analysis demonstrated that BNIP3L levels could act as an independent protective indicator of MM patient survival (HR = 0.79). Moreover, 261 co-expressed genes of BNIP3L were confirmed and found to be mainly involved in the adipocytokine signaling pathway. We preliminarily proved that downregulation of BNIP3L may play an important role in the occurrence and development of MM, and the promoting cancer capacity may be related to the pathway of adipocytokine signaling pathway.
多发性骨髓瘤(MM)是当今威胁人类健康的主要血液疾病之一。本研究旨在探讨 BCL-2/腺病毒 E1B 19kDa 相互作用蛋白 3 样(BNIP3L)在 MM 患者中的表达,并在计算机上探索其机制。使用免疫组织化学法对来自 MM 患者的 36 例骨髓样本和来自健康供体的 12 例骨髓样本进行 BNIP3L 表达分析。使用来自 Sequence Read Archive、Gene Expression Omnibus 和 ArrayExpress 数据库的微阵列或 RNA 测序数据评估 BNIP3L 在 MM 患者中的表达及其预后作用。鉴定 BNIP3L 的共表达基因进行富集和蛋白质-蛋白质相互作用(PPI)分析,以确定相关的信号通路。免疫组织化学表明,MM 患者骨髓中的 BNIP3L 表达明显低于健康供体骨髓中的 BNIP3L 表达。与健康供体相比,MM 患者的 BNIP3L mRNA 表达也明显降低。根据 694 例 MM 病例的总标准均数差(SMD),BNIP3L 下调的总 SMD 为-0.62[-1.17,-0.06],曲线下面积为 0.81[0.78,0.85]。总体生存分析表明,BNIP3L 水平可以作为 MM 患者生存的独立保护指标(HR=0.79)。此外,还证实了 BNIP3L 的 261 个共表达基因,这些基因主要参与脂肪细胞因子信号通路。我们初步证明 BNIP3L 的下调可能在 MM 的发生和发展中起重要作用,其促进癌症的能力可能与脂肪细胞因子信号通路有关。