Abstract
Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.
Highlights
MicroRNAs are a wide family of small non-coding RNAs that have emerged as key players in regulating the expression of target genes and are important in many biological processes [1]
The analysis showed that high expression of miR-221 was was significantly associated with poor overall survival (OS), whereas significantly associated with poor OS in both the survival methods
Despite a large degree of heterogeneity (I2 = 73%, p = 0.001), the results showed a significantly shorter progression-free survival (PFS) in patients with high expression of miR-222 (HR: 1.67, 95% confidence intervals (95% confidence intervals (CI)): 1.10–2.51, p < 0.015; Supplementary Figure S5A)
Summary
MicroRNAs (miRNAs) are a wide family of small non-coding RNAs that have emerged as key players in regulating the expression of target genes and are important in many biological processes [1]. A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. MiR-221 and miR-222 have been frequently identified as deregulated across different cancer types; their prognostic significance in cancer remains controversial In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers
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