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

AimColorectal 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. MethodsThis 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 I2 statistic. "Funnel plot", "Beggs statistical test", and "Eggers statistical test and graph" will be used to assess publication bias. Stata V.13 software will be employed for meta-analysis. Results and conclusionAccording 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.