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. 2021 Aug;246(15):1706-1720.
doi: 10.1177/15353702211010417. Epub 2021 Apr 25.

Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins

Mingfei Xu  1 , Chaoyue Liu  1 , Lulan Pu  1 , Jinrong Lai  2 , Jingjia Li  1 , Qianwen Ning  3 , Xin Liu  3 , Shishan Deng  1
Affiliations

Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins

Mingfei Xu et al. Exp Biol Med (Maywood). 2021 Aug.

Abstract

Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan-Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan-Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.

Keywords: Breast cancer; bioinformatics; biomarkers; cadherin; expression.

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Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Transcript levels of the BC-related cadherins in various cancers (Oncomine). Number of datasets included in the current study with statistically significant BC-related cadherins upregulation (red) or downregulation (blue). The thresholds: P-value≤ 0.01; fold change≥ 2; gene rank ≤ 10%; data type: mRNA. (A color version of this figure is available in the online journal.)
Figure 2.
Figure 2.
mRNA expression levels of the BC-related cadherins (UALCAN). (*P<0.05; **P<0.01; ***P<0.001) (A color version of this figure is available in the online journal.)
Figure 3.
Figure 3.
Immunohistochemistry staining images of BC-related cadherins proteins (HPA). (NA: no available data). (A color version of this figure is available in the online journal.)
Figure 4.
Figure 4.
Relationship between the BC-related cadherins mRNA levels and tumor stages (GEPIA). (A color version of this figure is available in the online journal.)
Figure 5.
Figure 5.
Relationship between BC-associated cadherins mRNA levels and tumor subclasses (UALCAN). (*P < 0.05; **P < 0.01; ***P < 0.001). (A color version of this figure is available in the online journal.)
Figure 6.
Figure 6.
OS (overall survival) of the BC-related cadherins (KM-Plotter). (A color version of this figure is available in the online journal.)
Figure 7.
Figure 7.
RFS (relapse-free survival) of the BC-related cadherins (KM-Plotter). (A color version of this figure is available in the online journal.)
Figure 8.
Figure 8.
Genetic changes, binding analyses, and neighboring gene network of the BC-related cadherins (cBioPortal). (a) Mutation analysis of CDHs in BC. (b) Protein–protein interaction network of CDHs. (c) Gene–gene interaction network of CDHs and 50 most frequently altered neighboring genes. (A color version of this figure is available in the online journal.)
Figure 9.
Figure 9.
Enrichment analysis of the BC-related cadherins and 50 most commonly altered neighboring genes in BC. (a, b, and c) bar-plot of GO enrichment in cellular component terms, biological process terms, and molecular function terms. (d) Bar-plot of KEGG pathway. (A color version of this figure is available in the online journal.)
Figure 10.
Figure 10.
Summary of the relationship between BC-related cadherins and BC. (A color version of this figure is available in the online journal.)
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