3.2 Comparison of high and low PD-L1 expression associated with clinical parameters
This study showed that high expression of PD-L1 in TCs was correlated with femal patients (OR,0.68; 95% CI: [0.56, 0.82]; P <0.001). Meta-analysis of twenty-three studies contrasting the smokers to non-smokers revealed that high PD-L1 expression in TCs was associated with non-smoker (OR, 0.62; 95% CI: [0.48, 0.79]; P <0.001). High expression of PD-L1 in TCs was observed in non-drinkers (OR, 0.69; 95% CI: [0.49, 0.98]; P =0.037) (Fig.2 ). However, the consequent meta-analysis suggested that the statistically significant association was disappeared between the expression of PD-L1 in TILs involving gender, smoking and drinking (Supplemental File 2 ).
There were no significant differences between the expression of PD-L1 in TCs and age, T status, M status, grade, or anatomical location. (Supplemental Fig.S3-S7) . Thirty studies were selected to identify whether the N status was associated with PD-L1 expression. The results showed that N+ patients were more likely to have high expression of PD-L1 when compared to N0 patients (OR, 1.34; 95% CI: [1.03, 1.74]; P =0.027)(Supplemental Fig.S8) .Tumor stages were grouped as stage I/II and stage III/IV that were used to assess the discrepancy in comparison of high/low expression. Seventeen studies were ultimately enrolled in meta-analysis. The result showed that patients with stage III/IV had high PD-L1 expression (OR, 1.41; 95% CI: [1.04, 1.90]; P =0.028)(Supplemental Fig.S9) . The significance was also observed in the association of high PD-L1 expression in TCs with high levels of PD-1 (OR,33.57; 95% CI: [2.08, 542.52]; P =0.024), and CD8+ (OR,5.03; 95% CI: [1.23, 20.50]; P =0.022)(Supplemental Fig.S10) . No significant association was found between PD-L1 expression on TILs and any clinicopathological variables (Supplemental File 2 ).