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

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.

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 I² 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.

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.

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.