Abstract

Background

Patients with advanced gastric cancer (GC) have poor prognoses despite getting multidisciplinary treatment. Tumor expression of Programmed Death-Ligand 1 (PD-L1) has been associated with unfavorable outcomes in gastrointestinal malignancies. The relationship between prognosis and PD-L1 expression in GC patients has been studied before with conflicting results. We intended to evaluate the prognostic significance of PDL1 in GC in terms of overall survivability based on previously published meta-analyses.

Methods

We performed an umbrella meta-analysis on previously published meta-analyses data over PubMed (January 01, 2016, to August 01, 2021), utilizing PRISMA guidelines, to investigate the association between PD-L1 expression and prognosis in GC patients. Review Manager (RevMan) 5.3 was used to estimate the effect size and 95% confidence interval (CI) using random-effects models and the inverse variance method. We also assessed the between-study heterogeneity (I²). We considered overall survival (OS) as the primary outcome. We calculated Hazard Ratio (HR) and obtained a forest plot and funnel plots considering a p-value < 0.05 as statistically significant.

Results

Of the total of 567 articles screened; 14 studies were assessed for eligibility. Out of which, three meta-analyses were included for umbrella review with a total of 8,419 sample size having PD-L1 positivity of 39%. A total of 40 primary studies conducted over a period of 14 years (2006-2019) were included in the 3 meta-analyses. All the 3 studies included in the umbrella review showed that PD-L1 positive expression was associated with low OS in GC with increased mortality (HR =1.44, 95% CI: 1.24 –1.68, P< 0.00001). Interstudy variability (I2) was 0%. (Figure)

Conclusions

Our findings reveal that the expression level of PD-L1 in gastric cancer has an inverse correlation with overall survivability and prognosis. Early identification of gene expression may help to tailor the treatment amongst patients with gastric cancer. It is obvious that PD-L1 positivity has both predictive & prognostic biomarker potential.