Ravegnini Gloria, Cargnin Sarah, Sammarini Giulia, Zanotti Federica, Bermejo Justo Lorenzo, Hrelia Patrizia, Terrazzino Salvatore, Angelini Sabrina
Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.
Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, 28100 Novara, Italy.
Cancers (Basel). 2019 Jul 11;11(7):970. doi: 10.3390/cancers11070970.
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. 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, = 0.003 and HR: 1.90, 95% CI: 1.43-2.54, < 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. 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.
大量证据表明，微小RNA（miRNA）可调节特定基因，增进了我们对蛋白质表达精细调控的认识。miR-221和miR-222在不同癌症类型中经常被发现表达失调；然而，它们在癌症中的预后意义仍存在争议。鉴于这些考虑因素，我们对已发表的数据进行了更新的系统评价和荟萃分析，以研究miR-221/222对癌症患者总生存期（OS）和其他次要结局的影响。我们对PubMed、Web of Knowledge和Cochrane图书馆数据库进行了系统检索。采用风险比（HR）和95%置信区间（95%CI）来评估关联强度。系统评价纳入了50项研究，分析了6086例患者。荟萃分析纳入了25项评估miR-221的研究和17项评估miR-222的研究，这些研究均评估了OS。miR-221和miR-222的高表达显著预示着较差的OS（HR分别为1.48，95%CI：1.14-1.93，P = 0.003；HR为1.90，95%CI：1.43-2.54，P < 0.001）。亚组分析显示，关于miR-221的研究结果不如关于miR-222的研究结果可靠。此外，miR-222的高表达还与较差的无进展生存期以及无疾病生存期（合并无复发生存期）相关。荟萃分析表明，miR-222的高表达与癌症患者的不良预后相关，而miR-221的意义仍不明确。鉴于现有结果存在局限性（包括显著的异质性以及部分癌症的研究数量有限），需要开展更多工作以全面阐明miR-221和miR-222在癌症预后中的作用。
