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Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer

BACKGROUND: Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongati...

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Autores principales: Li, Wan-Wan, Liu, Bin, Dong, Shu-Qing, He, Shi-Qing, Liu, Yu-Ying, Wei, Si-Yu, Mou, Jing-Yi, Zhang, Jia-Xin, Liu, Zhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965246/
https://www.ncbi.nlm.nih.gov/pubmed/35372047
http://dx.doi.org/10.3389/fonc.2022.856712
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author Li, Wan-Wan
Liu, Bin
Dong, Shu-Qing
He, Shi-Qing
Liu, Yu-Ying
Wei, Si-Yu
Mou, Jing-Yi
Zhang, Jia-Xin
Liu, Zhao
author_facet Li, Wan-Wan
Liu, Bin
Dong, Shu-Qing
He, Shi-Qing
Liu, Yu-Ying
Wei, Si-Yu
Mou, Jing-Yi
Zhang, Jia-Xin
Liu, Zhao
author_sort Li, Wan-Wan
collection PubMed
description BACKGROUND: Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongation and a novel key molecule in the poor prognosis of many cancers. However, its role in the development and progression of breast cancer remains unclear. METHODS: The transcript expression of CHPF in the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA), Gene Expression Omnibus (GEO) database was analyzed separately using the limma package of R software, and the relationship between CHPF transcriptional expression and CHPF DNA methylation was investigated in TCGA-BRCA. Kaplan-Meier curves were plotted using the Survival package to further assess the prognostic impact of CHPF DNA methylation/expression. The association between CHPF transcript expression/DNA methylation and cancer immune infiltration and immune markers was investigated using the TIMER and TISIDB databases. We also performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the clusterProfiler package. Western blotting and RT-PCR were used to verify the protein level and mRNA level of CHPF in breast tissue and cell lines, respectively. Small interfering plasmids and lentiviral plasmids were constructed for transient and stable transfection of breast cancer cell lines MCF-7 and SUM1315, respectively, followed by proliferation-related functional assays, such as CCK8, EDU, clone formation assays; migration and invasion-related functional assays, such as wound healing assay and transwell assays. We also conducted a preliminary study of the mechanism. RESULTS: We observed that CHPF was significantly upregulated in breast cancer tissues and correlated with poor prognosis. CHPF gene transcriptional expression and methylation are associated with immune infiltration immune markers. CHPF promotes proliferation, migration, invasion of the breast cancer cell lines MCF-7 and SUM1315, and is significantly enriched in pathways associated with the ECM-receptor interaction and PI3K-AKT pathway. CONCLUSION: CHPF transcriptional expression and DNA methylation correlate with immune infiltration and immune markers. Upregulation of CHPF in breast cancer promotes malignant behavior of cancer cells and is associated with poorer survival in breast cancer, possibly through ECM-receptor interactions and the PI3K-AKT pathway.
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spelling pubmed-89652462022-03-31 Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer Li, Wan-Wan Liu, Bin Dong, Shu-Qing He, Shi-Qing Liu, Yu-Ying Wei, Si-Yu Mou, Jing-Yi Zhang, Jia-Xin Liu, Zhao Front Oncol Oncology BACKGROUND: Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongation and a novel key molecule in the poor prognosis of many cancers. However, its role in the development and progression of breast cancer remains unclear. METHODS: The transcript expression of CHPF in the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA), Gene Expression Omnibus (GEO) database was analyzed separately using the limma package of R software, and the relationship between CHPF transcriptional expression and CHPF DNA methylation was investigated in TCGA-BRCA. Kaplan-Meier curves were plotted using the Survival package to further assess the prognostic impact of CHPF DNA methylation/expression. The association between CHPF transcript expression/DNA methylation and cancer immune infiltration and immune markers was investigated using the TIMER and TISIDB databases. We also performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the clusterProfiler package. Western blotting and RT-PCR were used to verify the protein level and mRNA level of CHPF in breast tissue and cell lines, respectively. Small interfering plasmids and lentiviral plasmids were constructed for transient and stable transfection of breast cancer cell lines MCF-7 and SUM1315, respectively, followed by proliferation-related functional assays, such as CCK8, EDU, clone formation assays; migration and invasion-related functional assays, such as wound healing assay and transwell assays. We also conducted a preliminary study of the mechanism. RESULTS: We observed that CHPF was significantly upregulated in breast cancer tissues and correlated with poor prognosis. CHPF gene transcriptional expression and methylation are associated with immune infiltration immune markers. CHPF promotes proliferation, migration, invasion of the breast cancer cell lines MCF-7 and SUM1315, and is significantly enriched in pathways associated with the ECM-receptor interaction and PI3K-AKT pathway. CONCLUSION: CHPF transcriptional expression and DNA methylation correlate with immune infiltration and immune markers. Upregulation of CHPF in breast cancer promotes malignant behavior of cancer cells and is associated with poorer survival in breast cancer, possibly through ECM-receptor interactions and the PI3K-AKT pathway. Frontiers Media S.A. 2022-03-15 /pmc/articles/PMC8965246/ /pubmed/35372047 http://dx.doi.org/10.3389/fonc.2022.856712 Text en Copyright © 2022 Li, Liu, Dong, He, Liu, Wei, Mou, Zhang and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Li, Wan-Wan
Liu, Bin
Dong, Shu-Qing
He, Shi-Qing
Liu, Yu-Ying
Wei, Si-Yu
Mou, Jing-Yi
Zhang, Jia-Xin
Liu, Zhao
Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title_full Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title_fullStr Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title_full_unstemmed Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title_short Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
title_sort bioinformatics and experimental analysis of the prognostic and predictive value of the chpf gene on breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965246/
https://www.ncbi.nlm.nih.gov/pubmed/35372047
http://dx.doi.org/10.3389/fonc.2022.856712
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