PCDHA1 High Expression is Associated With Poor Prognosis and Correlated With Immune Cell Infiltration in Breast Cancer.

INTRODUCTION: Breast cancer (BC) remains one of the biggest threats to women's health. Protocadherin gene Protocadherin Alpha 1 (PCDHA1) is abnormally highly expressed in breast cancer tissues. However, the biological role of PCDHA1 in breast cancer has not been fully elucidated and the relationship with the immune microenvironment needs to be further studied.

MATERIALS AND METHODS: TCGA-BRCA gene expression profiles were used to characterize PCDHA1. Kaplan-Meier method was used to estimate PCDHA1 prognosis potential. Gene set enrichment analysis (GSEA) analysis was performed to determine the signaling pathways altered by PCDHA1 aberrant expression. The correlations between PCDHA1 and immune cell infiltration levels were analyzed by CIBERSORT. Wilcoxon's rank-sum test was used to identify chemokine and chemokine receptors significantly associated with PCDHA1. The CCK8 assay and the transwell invasion assay were occupied to evaluate the effect of PCDHA1 overexpression on BC cells.

RESULTS: Survival analysis revealed PCDHA1 overexpression was associated with poor prognosis in BC. Enrichment analysis uncovered several metabolism pathways were activated by PCDHA1 overexpression. Moreover, PCDHA1 was positively correlated with activated NK cells but negatively correlated with resting NK cells infiltration. In addition, chemokines CCL28, CXCL17, and receptor CCR9 expression were associated with PCDHA1 overexpression. The CCK8 assay and the transwell invasion assay proved that PCDHA1 overexpression enhanced MCF-7 and MDA-MB-231 cell proliferation and invasion.

CONCLUSION: This study demonstrated that PCDHA1 effectively predicted BC prognosis. Upregulated PCDHA1 activated metabolism pathways, and promoted NK cells and chemokines. PCDHA1 overexpression enhanced BC cell proliferation and invasion. Therefore, an understanding of PCDHA1's function in BC may yield insights into the mechanisms of BC development.