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Expression and Clinical Significance of BCL2 Interacting Protein 3 Like in Multiple Myeloma.

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.

SUBMITTER: Li R

PROVIDER: S-EPMC8258758 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In our previous studies, we identified 12 multiple myeloma (MM)-associated antigens by serological analysis of tumor-associated antigens with a recombinant cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A-related transcript variant 1 that is specifically associated with MM. We examined its prognostic significance for the first time, by investigating the correlations between MMSA-8 expression and definite clinicopathological features. We quantitatively assessed MMSA-8 expression using qRT-PCR and western blot analysis in healthy donors and MM patients. The expression levels of MMSA-8 were upregulated with statistical significance in MM patients in contrast to those in healthy donors. The expression of MMSA-8 was also upregulated in relapsed patients compared with that in the complete remission (CR) group. Contrasting MMSA-8 expression levels in different patients with definite clinicopathological features suggested an association between MMSA-8 with unfavorable clinicopathological characteristics, such as international staging system (ISS) stage III, higher lactate dehydrogenase (LDH) levels and higher C-reactive protein (CRP) levels. The expression of MMSA-8 was also increased in patients with unfavorable cytogenetic and genetic abnormalities, including the presence of t(11;14), t(4;14), t(14;16), del(17p), del(13q) and p53 deletion, which was statistically significant. The expression of MMSA-8 exhibited significant variance in the treatment responses of the CR, PR, progression and relapse groups. Univariate and multivariate analyses revealed that high MMSA-8 values were associated with poorer progression-free survival (PFS) and overall survival (OS) in MM patients independently. In conclusion, our data indicated that MMSA-8 is an independent and unfavorable prognostic risk factor in MM; MMSA-8 is also a promising diagnostic and therapeutic target in MM patients, but further validation is needed.

Project description:ObjectiveThe present study aimed to detect A-kinase interacting protein 1 expression and further explore the association of A-kinase interacting protein 1 with clinical features and prognosis in patients with multiple myeloma.MethodsTotally, 152 de novo symptomatic patients with multiple myeloma and 30 healthy donors were enrolled. Bone marrow mononuclear cells derived plasma cells were collected from patients with multiple myeloma before initial treatment and from healthy donors on the enrollment, respectively, and then A-kinase interacting protein 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction. Treatment response (complete response and overall response rate) was assessed, and survival profiles (progression-free survival and overall survival) were calculated in patients with multiple myeloma.ResultsA-kinase interacting protein 1 protein/messenger RNA expressions were elevated in patients with multiple myeloma compared to healthy donors, and A-kinase interacting protein 1 (area under the curve: 0.809, 95% confidence interval: 0.726-0.891)/messenger RNA (area under the curve: 0.839, 95% confidence interval: 0.764-0.914) presented good value in differentiating patients with multiple myeloma from healthy donors. In patients with multiple myeloma, A-kinase interacting protein 1 /messenger RNA expressions negatively correlated with albumin while positively correlated with Beta-2-microglobulin, lactate dehydrogenase, International Staging System stage, and t (4;14). Meanwhile, there were 39 (25.7%) complete response patients, 113 (74.3%) noncomplete response patients, 112 (73.7%) overall response rate patients, and 40 (26.3%) nonoverall response rate patients. Complete response and overall response rates were decreased in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. Additionally, progression-free survival and overall survival were reduced in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1.ConclusionA-kinase interacting protein 1 exhibits the potency as a biomarker for multiple myeloma progression and prognosis, which implies the clinical application of A-kinase interacting protein 1 in multiple myeloma management.

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Expression and Clinical Significance of BCL2 Interacting Protein 3 Like in Multiple Myeloma.

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