Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Abstract

CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues at both mRNA and protein levels. In the in-house cohort, CDCP1 protein expression was related to several clinicopathological parameters, including age, ER status, PR status, molecular type, and survival status. Kaplan-Meier analysis and Cox regression analysis exhibited that CDCP1 was an important prognostic biomarker in BrCa. In addition, enrichment analysis uncovered that CDCP1 was not only involved in multiple oncogenic pathways, but correlated with overexpression of immune checkpoints. Overall, we reported that increased expression of CDCP1 is a favorable prognostic factor in patients with BrCa. In addition, the correlations between CDCP1 and immune checkpoints provide a novel insight into the adjuvant treatment for immune checkpoint blockade via targeting CDCP1.

Figure 1

Expression of CDCP1 in paratumor and BrCa tissues. (a) Comparison of CDCP1 mRNA expression in paratumor and BrCa tissues in the TCGA dataset based on data mining via UALCAN. (b) Comparison of CDCP1 protein expression in paratumor and BrCa tissues in the CPTAC dataset based on data mining via UALCAN. (c) Representative images revealing CDCP1 expression in tumor and paratumor tissues using anti-CDCP1 staining. (d) Expression levels of CDCP1 in tumor and paratumor tissues in the in-house cohort.

Figure 2

Expression of CDCP1 in BrCa tissues with various stages and subtypes. (a, b) Comparison of CDCP1 mRNA expression in BrCa tissues with various stages and subtypes in the TCGA dataset based on data mining via UALCAN. (c, d) Comparison of CDCP1 protein expression in BrCa tissues with various stages and subtypes in the CPTAC dataset based on data mining via UALCAN. (e, f) Comparison of CDCP1 protein expression in BrCa tissues with various stages and subtypes in the in-house cohort.

Figure 3

Prognostic value of CDCP1 in BrCa patients. (a, b, c) RFS, OS, and DMFS curves were plotted to assess the prognostic value of CDCP1 mRNA expression in BrCa using the Kaplan–Meier Plotter database. (d) Expression levels of CDCP1 in tumor tissues from alive and dead patients. (e) OS curves were plotted to evaluate the prognostic value of CDCP1 protein expression in the in-house cohort.

Figure 4

Enrichment analysis of PCGs of CDCP1 in BrCa. (a) Hallmark enrichment analysis of PCGs of CDCP1. (b) Wikipathways enrichment analysis of PCGs of CDCP1. (c) Heatmap showing PCGs expressions in the Wikipathways enrichment analysis. (d) Representative images revealing CDCP1 and EGFR expressions in tumor tissues using anti-CDCP1 and anti-EGFR staining. (e) Correlation between CDCP1 and EGFR in BrCa tissues in the in-house cohort.

Figure 5

Association between CDCP1 and the immune microenvironment in BrCa. (a) Correlations between CDCP1 and stromal score, immune score, and ESTIMATE score are estimated by the ESTIMATE method. (b) Correlations between CDCP1 and indicated gene expressions. (c) Heatmap showing immunomodulators expressions in BrCa tissues. (d) Heatmap showing TIICs abundance estimated by the CIBERSOR method in BrCa tissues.

Figure 6

Predictive value of CDCP1 for immunotherapy in BrCa cohort. (a) Expression levels of CDCP1 and PD-L1 in BrCa with various immunotherapeutic responses. (b) Comparison of predictive values of CDCP1 and PD-L1 in BrCa cohort.