Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.
Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.
Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.
Conclusion: Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.