RESUMO
Purpose: The prognostic role of programmed death-ligand 1 (PD-L1) in colorectal cancer remains unclear. We employed a meta-analysis to explore the prognostic value of PD-L1 and to ascertain the relationship between PD-L1 expression and clinicopathological characteristics in CRC patients. Methods: We systematically searched PubMed, Embase and the Cochrane Library until October 2018. Eligible studies about colorectal cancer that pay attention to PD-L1 expression and studies reporting survival information were included. In order to evaluate the prognostic role of PD-L1 for overall survival (OS) and recurrence-free survival (RFS)/disease-free survival (DFS), Hazard ratio (HR) with 95% confidence interval (CI) was used. Odds ratio (OR) with 95% CI was selected to appraise the correlation between PD-L1 with clinicopathological characteristics of colorectal cancer patients. Begg's funnel plot was used to assess publication bias. Results: Twelve studies involving 4344 patients published from 2013 to 2018 were included in this meta-analysis. Pooled results revealed that PD-L1 overexpression was relevant to shorter OS (HR 1.47, 95% CI =1.01-2.15, p=0.04) and shorter RFS/DFS (HR 1.47, 95% CI =1.01-2.15, p=0.04). Moreover, Patients with high expression of PD-L1 associated with inferior tumor stage (OR=0.57, 95% CI: 0.45, 0.74, p<0.0001) and Vascular invasion-negativity (OR=0.75, 95% CI: 0.6, 0.94, p=0.01). But the expression of PD-L1 is not related to age, sex, tumor location, tumor differentiation, pT stage, pN stage, MSI/MMR status. Conclusion: This meta-analysis revealed that PD-L1 can serve as a significant biomarker for negative prognosis and the adverse clinicopathological features of colorectal cancer and could facilitate the better management of individual patients.
RESUMO
PURPOSE: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. METHODS: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. RESULTS: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3' untranslated region. CONCLUSION: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.
