The Prognostic Value of PD-1/PD-L1 Expression on Tumor Cells and Tumor-Infiltrating Immune Cells in Patients with Colorectal Cancer: a Systematic Review and Meta-Analysis Protocol

Aim Colorectal cancer (CRC) is one of the most common cancers in the world. However, the role of immune checkpoint molecules, especially Programmed cell death protein 1 (PD-1) and Programmed cell death-ligand 1 (PD-L1), in the progression of CRC remains unclear. This systematic review and meta-analysis will investigate the prognostic significance of PD-1/PD-L1 expression on tumor-infiltrating immune cells and tumor cells in patients with colorectal cancer. Methods This protocol has been prospectively registered in the PROSPERO (registration NO. CRD42020156233). A comprehensive electronic search on PubMed/MEDLINE, Scopus, Web of Science (WOS), Embase and ProQuest will be conducted using a combination of MeSH terms of “programmed cell death 1”, “programmed cell death ligand 1”, “colorectal” and “cancer” between 1 January 1990 and 31 March 2021 with no language limitation. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment. The Newcastle-Ottawa Scale (NOS) for cohort studies will be used to assess the risk of bias. In the case of sufficient data, either random or fixed-effect models, will be used for meta-analysis. Statistical heterogeneity will be evaluated by 𝒳 2 test with the I 2 statistic. “Funnel plot”, “Begg’s statistical test”, and “Egger’s statistical test and graph” will be used to assess publication bias. Stata V.13 software will be employed for meta-analysis. Results and conclusion According to the meta-analysis of the aggregated data from the relevant primary studies, the relationship between expression of PD-1/PD-L1 and prognostic parameters, including progression-free survival and overall survival, will be reported. The results of the current study will be published in a peer-reviewed journal.