Prognostic and Clinicopathological Value of Programmed Death Ligand-1 in Breast Cancer: A Meta-Analysis

Abstract

Recently, the interest in programmed death ligand-1 (PD-L1) as a prognostic marker in several types of malignant tumors has increased. In the present meta-analysis, we aimed to explore the prognostic and clinicopathological value of PD-L1 in breast cancer. We searched Medline/PubMed, Web of Science, EMBASE, the Cochrane Library databases, and grey literature from inception until January 20, 2016. Studies concerning breast cancer that focused on PD-L1 expression and studies reporting survival data were included; two authors independently performed the data extraction. The pooled risk ratio (RR) and 95% confidence interval (CI) were assessed to determine the association between the clinicopathological parameters of patients and PD-L1 expression. Five studies involving 2061 patients were included in this meta-analysis. The results indicated that positive/higher PD-L1 expression was a negative predictor for breast cancer, with an RR of 1.64 (95% CI, 1.14–2.34) for the total mortality risk and an RR of 2.53 (95% CI, 1.78–3.59) for the mortality risk 10 years after surgery. Moreover, positive/higher PD-L1 expression was significantly associated with positive lymph node metastasis (RR, 1.33; 95% CI, 1.04–1.70), poor nuclear grade (RR, 1.24; 95% CI, 1.07–1.43), and negative estrogen receptor status (RR, 2.45; 95% CI, 1.31–4.60) in breast cancer patients. Our findings suggest that PD-L1 can serve as a significant biomarker for poor prognosis and the adverse clinicopathologic features of breast cancer and could facilitate the better management of individual patients.

PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma

“…The cut-off of more than 10% was selected in this study because it was associated with a statistically significant poorer DSS. As an immunosuppressive molecule promoting T-cell exhaustion, increased expression of PD-L1 should lead to a worse prognosis, as documented in several cancers (49)(50)(51)(52), and as it was likewise observed in this study. Contrary to this, an association between tumor PD-L1 expression and improved prognosis has also been reported in other cancers (53)(54)(55).…”

Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis

“…When we pooled the data together, none of the clinicopathological features (gender, differentiation, tumor depth, lymph node status and TNM stage) was associated with PD-L1 expression. The conclusion is not the same as conventional experiences of other tumors (36)(37)(38)(39). Differences might be caused by the mechanism of PD-L1 in ESCC, inadequate sample size or variable definitions of PD-L1 expression.…”

The prognostic time dependence of intra-tumoural IFNγ mRNA and protein in patients with breast cancer followed for 14 years after surgery and radiotherapy, without subsequent systemic therapy

“…Therefore, the association of elevated intra-tumoural IFN␥ protein in patients with poor outcome could indicate its pro-tumourigenic role only if supported by evidence of its increased signalling. The association of IFN␥ protein with the elevated disease risk obtained in the current study was in line with the reports that PD-L1, a protein upregulated by IFN␥, was also associated with poor survival in patients with breast cancer [24]. Taken together, the activity of IFN␥ in breast tumour might have been mediated by PD-L1, even though PD-L1 upregulation is also upregulated by other cytokines such as TNF␣ [25] and IL-1␤ [26].…”