Expert OpinionMicroRNAs (miRNAs) are single stranded, small, non-coding RNAs which are known to play an important role in many biological processes and are detectable in serum and plasma samples. Aberrant expression of several miRNAs (miR-155, miR-210, miR-126-5p, miR-370, miR-328, and miR-204) have been associated with outcome in acute myeloid leukemia (AML).1-6 Recently, low serum expression of miR-223 has been implicated in the development of AML.7-9
Guopan Yu, Nanfang Hospital, Guangzhou, CN, and team compared serum levels of miR-223 in 131 patients with AML and 70 healthy controls who had no cancer symptoms or clinical signs of any other disease.10 RNA was extracted from serum and reverse transcribed prior to quantitative real time polymerase chain reaction (qPCR) being performed for both miR-223 and for a control miRNA that had been spiked into the sample at a known concentration during RNA purification.
Key findings
- There was a significant reduction in expression of miR-223 in the AML group compared with the control group (p< 0.05)
- Receiver operating characteristic curve analysis demonstrated that miR-223 levels could differentiate AML from the controls with a sensitivity of 83.2% and a specificity of 81.4%
- Serum miR-223 levels were higher in the favorable than in the intermediate/unfavorable cytogenetic risk groups and in patients in who achieved complete remission (CR), whereas low miR-223 was more often associated with higher risk cytogenetics and blasts in bone marrow (Table 1)
- miR-223 expression levels pre- and post-induction chemotherapy were compared and the levels of miR-223 post-induction were higher than they had been at pre-induction in both the patients who had achieved CR (p< 0.01) and those who had not (p< 0.05)
- Overall survival (OS) and relapse-free survival at 5 years were significantly shorter for those patients who had lower miR-223 expression levels (p= 0.021 and p= 0.003, respectively)
- Univariate and multivariate analysis showed that miR-223 is an independent predictor of OS in patients with AML (risk ratio [RR] 3.54; 95% confidence interval [CI], 1.47–5.79; p= 0.016 and RR 4.25; 95% CI, 1.29–7.38; p= 0.011, respectively)
- There was no association between miR-223 expression and age, gender, white blood cells, or platelets
Table 1: Serum miR-223 expression in AML cases
|
Patients (n= 131) |
Low miR-223 (n= 69) |
High miR-223 (n= 62) |
p value |
|
|
Cytogenetics Favorable Intermediate Unfavorable |
52 61 18 |
16 38 15 |
36 23 3 |
< 0.0001 |
|
Complete remission Yes No |
55 76 |
20 49 |
35 27 |
0.0015 |
|
Blasts in bone marrow < 50% ≥ 50% |
54 77 |
21 48 |
33 29 |
0.0081 |
Guopan Yu and colleagues state that their work is in agreement with previous work on miR-223 in AML.7-9 miR-223 regulates the equilibrium between expansion and differentiation in hematopoietic stem and progenitor cells, and expression of miR-223 leads to the production of red blood cells, T cells and B cells. Expression of miR-223 inhibits cell proliferation and increases apoptosis in AML cell lines, and knocking down miR-223 increases the frequency of myeloid progenitors. The authors discussed how decreased expression of miR-223 seems to be associated with nasopharyngeal carcinoma, cervical cancer, gallbladder cancer, hepatocellular carcinoma, and breast cancer, yet increased expression is seen in gastric cancer, colon cancer, and non-small cell lung cancer.10 The group conclude that miR-223 may be able to be used as diagnostic tool and as a predictor of poor patient outcome in patients with AML.
