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Expression and Clinical Significance of BCL2 Interacting Protein 3 Like in Multiple Myeloma
Ruolin Li1, Gang Chen2, Yiwu Dang2
1Department of Scientific Research, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
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.
Insights
BCL-2/adenovirus E1B 19 kDa-interacting protein 3-like (BNIP3L) is significantly downregulated in multiple myeloma (MM) patients. Lower BNIP3L levels indicate a protective factor for MM patient survival, potentially linked to the adipocytokine signaling pathway.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Multiple myeloma (MM) is a significant hematologic malignancy.
- Understanding the molecular mechanisms underlying MM pathogenesis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the expression levels of BCL-2/adenovirus E1B 19 kDa-interacting protein 3-like (BNIP3L) in patients with multiple myeloma.
- To explore the potential mechanisms and prognostic significance of BNIP3L in MM.
Main Methods:
- Immunohistochemistry was used to analyze BNIP3L protein expression in bone marrow samples from MM patients and healthy donors.
- Publicly available microarray and RNA sequencing data were analyzed to assess BNIP3L mRNA expression and its prognostic value.
- Bioinformatic analyses, including gene co-expression, enrichment, and protein-protein interaction (PPI) analyses, were performed to identify associated signaling pathways.
Main Results:
- BNIP3L expression was significantly lower in the bone marrow of MM patients compared to healthy donors at both protein and mRNA levels.
- Meta-analysis of 694 MM cases revealed a significant downregulation of BNIP3L (SMD = -0.62) with high diagnostic accuracy (AUC = 0.81).
- Lower BNIP3L levels were identified as an independent protective factor for MM patient survival (HR = 0.79).
- Co-expression analysis identified 261 genes associated with BNIP3L, primarily involved in the adipocytokine signaling pathway.
Conclusions:
- Downregulation of BNIP3L plays a potential role in the occurrence and development of multiple myeloma.
- The oncogenic capacity associated with BNIP3L downregulation may be linked to the adipocytokine signaling pathway.
- BNIP3L serves as a potential prognostic biomarker for multiple myeloma.
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