Increased expression of P-cadherin is an indicator of poor prognosis in breast cancer: a systematic review and meta-analysis

Sridhar, Sriya; Rajesh, Christabelle; Jishnu, Padacherri Vethil; Jayaram, Pradyumna; Kabekkodu, Shama Prasada

doi:10.1007/s10549-019-05477-5

Cited by 11 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19,20 A recent study revealed a strong association between high-expressing CDH3 and BC, and an inverse correlation between high-expressing CDH3 and poor BC subtype prognosis. 21 In our study, there was lower expression of CDH3 mRNA and protein in BC tissues when compared to healthy tissues. Moreover, elevated CDH3 levels were significantly related to poor OS and RFS in BC patients.…”

Section: Discussionsupporting

confidence: 40%

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

Xu¹,

Liu²,

Pu³

et al. 2021

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 40%

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

Xu¹,

Liu²,

Pu³

et al. 2021

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…A recently published systematic review which included 11 studies supports this finding. 28 It was found that the overexpression of P-cadherin is linked with adverse prognosis of BC, even though the prognosis of survival was not affected by the subtype of BC. Different subtypes of BC are treated differently; thus, the prognosis of P-cadherin in various subtypes of BC may not be easy to evaluate.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer prognosis and P-cadherin expression: systematic review and study-level meta-analysis

Lin

Chen

et al. 2020

BMJ Support Palliat Care

View full text Add to dashboard Cite

ObjectiveP-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We conducted a study-level meta-analysis to determine whether P-cadherin expression can help predict prognosis in BC.MethodsA systematic literature search was performed to review eligible studies and clarify the relationship between P-cadherin overexpression and overall survival (OS), disease-free survival (DFS), pathological features, molecular subtypes and molecular phenotypes in BC.ResultsThirty-one studies including 12 332 patients were included. P-cadherin overexpression was correlated with significantly worse OS (HR=1.77, p<0.00001) and DFS (HR=1.96, p<0.00001) than P-cadherin-negative. P-cadherin overexpression could lead to high histological grade (OR=3.33, p<0.00001) and lymph node metastasis (OR=1.62, p<0.00001). Moreover, P-cadherin overexpression was associated with low odds of the luminal A subtype and high odds of the human epidermal growth factor receptor-2 (HER2)-positive and triple-negative subtypes. P-cadherin expression led to low expression of oestrogen and progesterone receptor (OR=0.37 and OR=0.36, respectively, both p<0.00001) and high expression of HER2 (OR=2.31, p<0.00001), Ki-67 (OR=2.79, p<0.00001), epidermal growth factor receptor (OR=5.85, p<0.00001) and cytokeratin 5/6 (OR=6.79, p<0.00001).ConclusionsP-cadherin was found to be associated with invasiveness and metastasis. P-cadherin expression can probably be a useful biomarker for predicting poor survival and may act as an independent prognostic predictor.

show abstract

“…8c). Expression of E-cadherin and P-cadherin in the same cell is indicative of an invasive, metastatic tumor cell 37, 38 . To determine whether the protein expression was changed, we measured epithelial cell specific E-cadherin and P-cadherin expression in primary tumors by immunofluorescence and observed decreased E-cadherin and increased P-cadherin expression in DN-Wnt1 and K8iKOR-Wnt1 primary tumors compared to Wnt1 tumors (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, the Ewald lab reported E-cadherin loss is required for metastatic invasion, and its re-expression is necessary to promote metastatic growth 35 . Furthermore, upregulation of P-cadherin and its co-expression with E-cadherin in the primary tumor is a marker of more aggressive, metastatic breast tumors [36][37][38][39] . To identify correlation of cadherin expression with IGF-1R expression in patient tumors, we analyzed the METABRIC dataset and identified significant inverse correlation of Pcadherin expression with IGF-1R expression.…”

Section: Cell Adherence Is Dysregulated By Enhanced P-cadherin Expression In Epithelial Cells With Reduced Igf-1r Functionmentioning

confidence: 99%

“…Furthermore, upregulation of P-cadherin and its co-expression with E-cadherin in the primary tumor is a marker of more aggressive, metastatic breast tumors (38)(39)(40)(41). To determine if cadherin expression changes with IGF-1R expression in patient tumors, we analyzed the METABRIC dataset and identified an inverse correlation of P-cadherin and IGF-1R expression.…”

Section: Cell Adherence Is Dysregulated By Enhanced P-cadherin Expression In Epithelial Cells With Reduced Igf-1r Functionmentioning

confidence: 99%

See 1 more Smart Citation

Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

Obr

Chang

Ciliento

et al. 2021

Preprint

View full text Add to dashboard Cite

The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted correlation gene network analysis (WCGNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.

show abstract

Increased expression of P-cadherin is an indicator of poor prognosis in breast cancer: a systematic review and meta-analysis

Cited by 11 publications

References 56 publications

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

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

Breast cancer prognosis and P-cadherin expression: systematic review and study-level meta-analysis

Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

Contact Info

Product

Resources

About