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Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma
Xianjuan Shen1, Yan Ye2, Jing Qi1
1Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
Background:
miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer.
Methods:
We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR.
Results:
Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with β2M, λ light and κ light chain concentration (r=0.480, p=0.0003; r=0.560, p<0.0001; r=0.560, p<0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r=0.247, p=0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR-4449, λ light chain, and β2M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined.
Conclusions:
The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.
Insights
Serum miR-4449 levels are significantly elevated in multiple myeloma (MM) patients compared to healthy individuals. This microRNA shows potential as a novel biomarker for auxiliary diagnosis of MM.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) regulate crucial biological processes, including cell growth and apoptosis, implicating them in cancer development.
- Multiple Myeloma (MM) is a cancer of plasma cells, and understanding its molecular underpinnings is critical for diagnosis and treatment.
Purpose of the Study:
- To investigate the expression profile of miRNAs in CD138+ primary multiple myeloma cells.
- To evaluate the diagnostic potential of serum miR-4449 as a biomarker for multiple myeloma.
Main Methods:
- Microarray analysis and RT-qPCR were used to identify perturbed miRNAs in MM cells.
- Serum and bone marrow miR-4449 levels were quantified using RT-qPCR in MM patients and healthy controls.
Main Results:
- A significant number of miRNAs were found to be differentially expressed in MM patients.
- Serum miR-4449 levels were significantly higher in MM patients compared to healthy controls (p<0.0001).
- Serum miR-4449 demonstrated strong diagnostic accuracy (AUC=0.885) and correlated with MM disease markers like β2M and light chains.
Conclusions:
- Serum miR-4449 is significantly upregulated in multiple myeloma patients.
- miR-4449 holds promise as a valuable auxiliary diagnostic biomarker for multiple myeloma.
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