TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets

Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases co...

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Published in:PloS one 2020-06, Vol.15 (6), p.e0233884-e0233884
Main Authors: Wong, Kah Keng, Hussain, Faezahtul Arbaeyah
Format: Article
Language:English
Subjects:
Antibodies
Appendicitis
Biology and Life Sciences
Breast cancer
Cancer genetics
Cancer treatment
Cell transformation
Colorectal cancer
Criminal investigation
Data mining
Datasets
Development and progression
DNA microarrays
EDTA
Epithelium
Estrogen receptors
Estrogens
Ethanol
Females
Gene expression
Gene set enrichment analysis
Genes
Genetic aspects
Genomes
Genomics
Health aspects
Immunohistochemistry
Ion channels
Lymph nodes
Lymphatic system
Medicine and Health Sciences
Mesenchyme
Parameters
Pathology
Patients
Phenols (Class of compounds)
Prostate cancer
Proteins
Receptors
Research and Analysis Methods
Solid tumors
Stem cells
Therapeutic targets
Transcription
Transient receptor potential proteins
Tumors
Values
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description Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10.sup.-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4.sup.+ ; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4.sup.+ ; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p
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Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10.sup.-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4.sup.+ ; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4.sup.+ ; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p&lt;0.01 and false discovery rate&lt;0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). 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Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10.sup.-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4.sup.+ ; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4.sup.+ ; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p&lt;0.01 and false discovery rate&lt;0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). 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Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10.sup.-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4.sup.+ ; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4.sup.+ ; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p&lt;0.01 and false discovery rate&lt;0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32484822</pmid><doi>10.1371/journal.pone.0233884</doi><tpages>e0233884</tpages><orcidid>https://orcid.org/0000-0001-7359-6202</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antibodies
Appendicitis
Biology and Life Sciences
Breast cancer
Cancer genetics
Cancer treatment
Cell transformation
Colorectal cancer
Criminal investigation
Data mining
Datasets
Development and progression
DNA microarrays
EDTA
Epithelium
Estrogen receptors
Estrogens
Ethanol
Females
Gene expression
Gene set enrichment analysis
Genes
Genetic aspects
Genomes
Genomics
Health aspects
Immunohistochemistry
Ion channels
Lymph nodes
Lymphatic system
Medicine and Health Sciences
Mesenchyme
Parameters
Pathology
Patients
Phenols (Class of compounds)
Prostate cancer
Proteins
Receptors
Research and Analysis Methods
Solid tumors
Stem cells
Therapeutic targets
Transcription
Transient receptor potential proteins
Tumors
Values
title TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets
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