Abstract
Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19–2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06–2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70–2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed cancer for males in 105 countries including North and South America, Western Europe and Australia [1]
The majority of PCa cases are localized disease with very high survival rate after initial treatment (∼100% 5-year survival), but recurrence may occur in about 40% as biochemical recurrence (BCR) or distant metastasis that has a significantly poorer prognosis (∼30% 5-year survival) [2]
Prognostic factor studies were prone to selective reporting in that miRNAs with insignificant findings might not be reported [24]; a high-sensitivity approach was used in the search strategy as shown in Supplementary Table ST 1
Summary
Prostate cancer (PCa) is the most commonly diagnosed cancer for males in 105 countries including North and South America, Western Europe and Australia [1]. The majority of PCa cases are localized disease with very high survival rate after initial treatment (∼100% 5-year survival), but recurrence may occur in about 40% as biochemical recurrence (BCR) or distant metastasis that has a significantly poorer prognosis (∼30% 5-year survival) [2]. Prognosis is predicted by considering cancer stage, Gleason score, prostate-specific antigen (PSA) level, patient’s health condition, treatment choice and treatment response [4]. These clinicopathological factors still have certain limitations. PSA lacks specificity and BCR, defined by rise in PSA level following prostatectomy or radiotherapy, does not necessarily predict clinical
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