MicroRNA-223 expression is uniformly down-regulated in B cell lymphoproliferative disorders and is associated with poor survival in patients with chronic lymphocytic leukemia

Abstract

MicroRNA-223 (miR-223) expression has been demonstrated to be stage-specific in B cell differentiation and associated with the outcome of chronic lymphocytic leukemia (CLL). However, the expression pattern of miR-223 in B cell lymphoproliferative disorders and its association with the outcome of Chinese patients with CLL have not been investigated. In this study, we demonstrated that miR-223 expression was significantly decreased in CLL, mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). In CLL, miR-223 expression decreased significantly with progression from early to advanced clinical stages and was significantly lower in patients with elevated β(2)-microglobulin, unmutated immunoglobulin variable heavy chain (IgVH) gene or with disease progression or death. Using a cut-off determined by receiver operating characteristic (ROC) analysis optimizing concordance with IgVH mutational status, miR-223-negative and -positive groups were defined for 22 and 31 patients, respectively. The median progression-free survival (PFS) and overall survival of the miR-223-negative group were 13 and 40 months, respectively, significantly shorter than for the miR-223-positive group (both not reached; p = 0.002 and p = 0.018, respectively). Multivariate analysis revealed that the absence of miR-223 was the only independent factor capable of predicting shorter PFS. In conclusion, miR-223 is uniformly down-regulated in B-LPDs and is a useful prognostic factor for patients with CLL.

MicroRNAs in chronic lymphocytic leukemia: miRacle or miRage for prognosis and targeted therapies?

“…Several of the miRNAs from this original signature could be confirmed, including increased expression of miR-15a 31,32 and miR-16 31 , and decreased expression of miR-29a 31 and miR-29b 33,34 as being associated with unmutated IGHV, and decreased levels of miR-29c 32,33,35,36 and miR-223 32,33,35–37 as being associated with unmutated IGHV and with increased expression of ZAP70, CD38 and B2M. One miRNA that was not included in the original signature, but that was repeatedly reported to correlate with poor prognostic markers (unmutated IGHV and increased expression of ZAP70, CD38 and B2M) is miR-150.…”

The mystery of chronic lymphocytic leukemia (CLL): Why is it absent in Asians and what does this tell us about etiology, pathogenesis and biology?

“…There are, unfortunately, no studies of familial CLL in Asians. Most data suggest no important differences between Asians and persons of predominately European descent with CLL [103][104][105][106][107]. An exception is a study from Chim and colleagues who reported similar methylation of miR-9-2, a member of the miR-9 gene family, identified as tumor suppressor miRNA in normal CD19+ B-cells and CLL B-cells in Hong Kong Chinese.…”

The effect of circulating miR-223 on surveillance of different cancers: a meta-analysis

“…The literature search included 10 studies eligible in the meta-analysis (Figure 1), 6 from China13,17,18,21–23 and 1 each from France,24 United States,15 Japan,19 and Belgium 20. The studies involved a total of 1,002 patients with cancer, with mean sample size of 1,002 patients (range: 46–180).…”

“…MiR-223, a common tumor-associated microRNA, has been reported to be dysregulated in various human tumors, such as hepatocellular carcinoma,9 colorectal carcinoma,10 osteosarcoma,11 gastric cancer,12 and chronic lymphocytic leukemia 13. Abnormal expression of miR-223 in cancerous tissue has confirmed it as an important player in tumorigenesis of cancers 14.…”