Abstract
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.
Keywords
Abbreviations:
BC (Breast cancer), TNBCs (triple-negative breast cancers), PCDHA1 (Protocadherin Alpha 1), CSE (conserved sequence elements), CNR (cadherin-related neuronal receptor), TCGA (the Cancer Genome Atlas), GSEA (Gene set enrichment analysis), MSigDB (Molecular Signatures Database), DMEM (Dulbecco's Modified Eagle's/Eagle Medium), FBS (fetal bovine serum), CCK8 (Cell counting Kit-8)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 09, 2023
Accepted:
February 2,
2023
Received in revised form:
January 28,
2023
Received:
July 11,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
