Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.

Abstract

The value of human leukocyte antigen (HLA; also known as major histocompatibility complex) class I expression for the prediction of breast cancer survival outcomes remains unclear. We conducted a meta-analysis to explore the prognostic significance of this expression. We searched electronic databases to identify reports on associations of HLA class I protein or mRNA expression with survival outcomes and clinicopathological factors in the breast cancer context. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to conduct a quantitative meta-analysis. The sample comprised eight studies involving 3590 patients. Only the classical HLA class Ia (HLA-ABC) molecules studies were included in this meta-analysis. Elevated HLA class I protein expression was found to be significantly related to better disease-free survival (DFS) (HR 0.58, 95% CI 0.35-0.95, P=0.03), particularly among patients with triple-negative breast cancer (TNBC) (HR 0.31, 95% CI 0.18-0.52, P <0.001), but not to overall survival. It was also associated with estrogen receptor (ER) negativity (OR 1.71, 95% CI 1.24-2.35, P=0.001), progesterone receptor (PR) negativity (OR 1.49, 95% CI 1.22-1.81, P<0.001), human epidermal growth factor receptor 2 (HER2) positivity (OR 1.51, 95% CI 1.18-1.94, P=0.001), TNBC (OR 1.68, 95% CI 1.15-2.45, P <0.01), high Ki-67 indices (OR 2.06, 95% CI 1.62-2.61, P <0.001), and high nuclear grades (OR 2.67, 95% CI 2.17-3.29, P <0.001). This meta-analysis demonstrated that enhanced HLA class I protein expression is significantlyassociated with the better DFS of patients with breast cancer, especially TNBC, as well as with ER and PR negativity, HER2 positivity, TNBC, and high Ki-67 indices and nuclear grades. The immune target HLA class I may serve as a prognostic indicator for breast cancer.