Dataset Information

Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores.

ABSTRACT:

Purpose

PR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed.

Methods

In this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression.

Results

ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER+/PR+/HER2- and ER+/PR-/HER2- groups.

Conclusions

In conclusion, this study indicated in ER+/HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation.

SUBMITTER: Hu T

PROVIDER: S-EPMC8141178 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores.

Hu Taobo T Chen Yan Y Liu Yiqiang Y Zhang Danhua D Pan Jiankang J Long Mengping M

BMC medical research methodology 20210522 1

<h4>Purpose</h4>PR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed.<h4>Methods</h4>In this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression.<h4>Results</h4>ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a com ...[more]

PMID: 34022815

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Project description:BackgroundTreatment strategies for various subtypes of breast cancer (BC) are different based on their distinct molecular characteristics. Therefore, it is very important to identify key differentially expressed genes (DEGs) between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.MethodsGene expression profiles of GSE22093 and GSE23988 were obtained from the Gene Expression Omnibus database. There were 74 ER-positive/HER2-negative BC tissues and 85 ER-negative/HER2-negative BC tissues in the two profile datasets. DEGs between ER-positive/HER2-negative tissues and ER-negative/HER2-negative BC tissues were identified by the GEO2R tool. The common DEGs among the two datasets were detected with Venn software online. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathways and gene ontology terms. Then, the protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with the Search Tool for the Retrieval of Interacting Genes. Of the proteins in the PPI network, Molecular Complex Detection plug-in analysis identified nine core upregulated genes and one core downregulated gene. UALCAN and Gene Expression Profiling Interactive Analysis were applied to determine the expression of these 10 genes in BC. Furthermore, for the analysis of overall survival among those genes, the Kaplan-Meier method was implemented.ResultsNinety-three common DEGs (63 upregulated and 30 downregulated) were identified. KEGG pathway enrichment analysis showed that upregulated DEGs were particularly enriched in the progesterone-mediated oocyte maturation pathway. In addition, PGR might be a prognostic biomarker for ER-positive/HER2-negative BC. CCND1 is a poor prognostic biomarker for ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Moreover, TFF1, AGR2 and EGFR might be predictive biomarkers of node metastasis in ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.ConclusionsCCND1, AGR2, PGR, TFF1 and EGFR are the key DEGs between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Further studies are required to confirm the functions of the identified genes.

Dataset Information

Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores.

Purpose

Methods

Results

Conclusions

Publications

Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores.

Similar Datasets

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