The prevalence and prognostic and clinicopathological value of PD-L1 and PD-L2 in renal cell carcinoma patients: a systematic review and meta-analysis involving 3,389 patients

BACKGROUND: The research of the prognostic and clinicopathologic values of programmed cell death ligand 1/2 (PD-L1/2) in renal cell carcinoma (RCC) patients has been mired by a dearth of studies and considerable controversy. We thus conducted a systematic review and meta-analysis to report the prevalence and prognostic and clinicopathological value of programmed cell death ligand 1 (PD-L1) and programmed cell death-legend 2 (PD-L2) in RCC patients. METHODS: The PubMed, Cochrane Library, EMBASE databases were searched to find human studies limited to English language literature published through October 1, 2019. Using random or fixed effects models, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to explore the prognostic value of PD-Ls expression, while odds ratios (ORs) and 95% CIs were evaluated to investigate clinicopathological parameters. The protocol of the study was registered in PROSPERO (CRD42019135199). RESULTS: After pooling all 16 eligible studies comprising 3,389 patients, we found that the overall prevalence of PD-L1 and PD-L2 in RCC patients was 27% and 39%, respectively. Furthermore, PD-L1 over-expression was a strong negative predictor for overall survival (OS), disease-free survival/progression-free survival (DFS/PFS), and cancer-specific survival (CSS) in renal cell carcinoma patients (HR =2.86, 95% CI: 1.83–4.47, P<0.001; HR =2.64, 95% CI: 1.99–3.52, P<0.001; HR =2.78, 95% CI: 2.17–3.56, P<0.001). Meanwhile, PD-L2 over-expression was only a weak negative predictor for CSS (HR =1.66, 95% CI: 1.05–2.65, P<0.05). Subgroup analysis showed that Caucasians had worse OS (HR =3.60, 95% CI: 1.77–7.33, P<0.001), PFS (HR =3.56, 95% CI: 2.44–5.18, P<0.001), and CSS (HR =3.13, 95% CI: 2.37–4.14, P<0.001) than Asians. PD-L1 was a strong indicator for worse prognosis (P<0.05 for all), while PD-L2 over-expression was only associated with sarcomatoid features (presence vs. absence, OR =1.80, 95% CI: 1.13–2.86, P=0.014). Notably, PD-L1 overexpression was more prevalent in women (male vs. female, OR =0.68, 95% CI: 0.51–0.90, P=0.006). CONCLUSIONS: Higher PD-L1 expression is more closely associated with poor prognosis and more advanced clinicopathological features in RCC patients than PD-L2, especially in women and Caucasian patients. PD-L2 was a weak negative predictor of poor CSS of RCC and was not a prompt for the metastasis of RCC.