PIWI family proteins as prognostic markers in cancer: a systematic review and meta-analysis

• Published in: Cellular and molecular life sciences : CMLS Vol. 77; no. 12; pp. 2289 - 2314
• Main Authors: Mentis, Alexios-Fotios A., Dardiotis, Efthimios, Romas, Nicholas A., Papavassiliou, Athanasios G.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2020; Springer Nature B.V
• Subjects: Argonaute Proteins - metabolism; Biochemistry; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cell Biology; Confidence intervals; Disease Progression; Gene expression; Germ cells; Heterogeneity; Humans; Life Sciences; Medical prognosis; Meta-analysis; Metastases; metastasis; mortality; mRNA; Neoplasms - metabolism; Neoplasms - pathology; P elements; Prognosis; Proportional Hazards Models; protein synthesis; Proteins; Regression analysis; Review; RNA, Messenger - metabolism; Statistical analysis; statistical models; systematic review; Survival analysis; Systematic review; piRNAs; PIWI family protein; Cancer; Meta-analysis
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-019-03403-y

Background P-element-induced-wimpy-testis-(PIWI)-like proteins are implicated in germ cells’ regulation and detected in numerous cancer types. In this meta-analysis, we aimed to associate, for the first time, the prognosis in cancer patients with intratumoral expression of PIWI family proteins. Methods PubMed, Embase, and Web of Knowledge databases were searched, and studies investigating the association between intratumoral mRNA or protein expression of different PIWI family proteins and survival, metastasis, or recurrence of various cancer types were reviewed. Study qualities were assessed using the REMARK criteria. Studies’ heterogeneity was evaluated using I 2 index and Cochran Q test. Publication bias was assessed by funnel plots and Egger’s regression. Pooled hazard ratios (HR) with 95% confidence intervals (95% CIs) were calculated for different PIWI family proteins separately. Specifically, log of calculated HR was pooled using random-effects model. Results Twenty-six studies (4299 participants) were included. The pooled HR of mortality in high versus low expression of PIWIL1, PIWIL2, and PIWIL4 was 1.87 (95% CI: 1.31–2.66, p  < 0.05), 1.09 (95% CI: 0.58–2.07, p  = 0.79), and 0.44 (95% CI: 0.25–0.76, p  < 0.05), respectively. The pooled HR of recurrence in high versus low expression of PIWIL1 and PIWIL2 was 1.72 (95% CI: 1.20–2.49, p  < 0.05) and 1.98 (95% CI: 0.65–5.98, p  = 0.23), respectively. Conclusions Highly variable results were observed for different cancer types. Higher PIWIL1 and lower piwil4 and PIWIL4 expression levels could potentially indicate worse prognosis in cancer. These proteins’ expressions could be used for personalized prognosis and treatment in the future.