PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation

Background: Glucose metabolism in breast cancer has a potential effect on tumor progression and is related to the immune microenvironment. Thus, this study aimed to develop a glucose metabolism–tumor microenvironment score to provide new perspectives on breast cancer treatment. Method: Data were acq...

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Main Authors: Yidong Zhang, Hang Xu, Xuedan Han, Qiyi Yu, Lufeng Zheng, Hua Xiao
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003930
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author Yidong Zhang
Hang Xu
Xuedan Han
Qiyi Yu
Lufeng Zheng
Hua Xiao
author_facet Yidong Zhang
Hang Xu
Xuedan Han
Qiyi Yu
Lufeng Zheng
Hua Xiao
author_sort Yidong Zhang
collection DOAJ
description Background: Glucose metabolism in breast cancer has a potential effect on tumor progression and is related to the immune microenvironment. Thus, this study aimed to develop a glucose metabolism–tumor microenvironment score to provide new perspectives on breast cancer treatment. Method: Data were acquired from the Gene Expression Omnibus and UCSC Xena databases, and glucose-metabolism-related genes were acquired from the Gene Set Enrichment Analysis database. Genes with significant prognostic value were identified, and immune infiltration analysis was conducted, and a prognostic model was constructed based on the results of these analyses. The results were validated by in vitro experiments with MCF-7 and MCF-10A cell lines, including expression validation, functional experiments, and bulk sequencing. Single-cell analysis was also conducted to explore the role of specific cell clusters in breast cancer, and Bayes deconvolution was used to further investigate the associations between cell clusters and tumor phenotypes of breast cancer. Results: Four significant prognostic genes (PMAIP1, PGK1, SIRT7, and SORBS1) were identified, and, through immune infiltration analysis, a combined prognostic model based on glucose metabolism and immune infiltration was established. The model was used to classify clinical subtypes of breast cancer, and PMAIP1 was identified as a potential critical gene related to glucose metabolism in breast cancer. Single-cell analysis and Bayes deconvolution jointly confirmed the protective role of the PMAIP1+ luminal cell cluster.
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publishDate 2025-02-01
publisher Elsevier
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series Translational Oncology
spelling doaj-art-f2a1f1650bdc4f9c8697f753fb5468a32025-01-22T05:41:33ZengElsevierTranslational Oncology1936-52332025-02-0152102267PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validationYidong Zhang0Hang Xu1Xuedan Han2Qiyi Yu3Lufeng Zheng4Hua Xiao5School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China; School of Pharmacy, Queen's University of Belfast, Belfast, Northern Ireland, United KingdomSchool of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China; Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaMellon College of Science, Carnage Mellon University, Pittsburgh, Pennsylvania, USASchool of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China; Corresponding authors.Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; Corresponding authors.Background: Glucose metabolism in breast cancer has a potential effect on tumor progression and is related to the immune microenvironment. Thus, this study aimed to develop a glucose metabolism–tumor microenvironment score to provide new perspectives on breast cancer treatment. Method: Data were acquired from the Gene Expression Omnibus and UCSC Xena databases, and glucose-metabolism-related genes were acquired from the Gene Set Enrichment Analysis database. Genes with significant prognostic value were identified, and immune infiltration analysis was conducted, and a prognostic model was constructed based on the results of these analyses. The results were validated by in vitro experiments with MCF-7 and MCF-10A cell lines, including expression validation, functional experiments, and bulk sequencing. Single-cell analysis was also conducted to explore the role of specific cell clusters in breast cancer, and Bayes deconvolution was used to further investigate the associations between cell clusters and tumor phenotypes of breast cancer. Results: Four significant prognostic genes (PMAIP1, PGK1, SIRT7, and SORBS1) were identified, and, through immune infiltration analysis, a combined prognostic model based on glucose metabolism and immune infiltration was established. The model was used to classify clinical subtypes of breast cancer, and PMAIP1 was identified as a potential critical gene related to glucose metabolism in breast cancer. Single-cell analysis and Bayes deconvolution jointly confirmed the protective role of the PMAIP1+ luminal cell cluster.http://www.sciencedirect.com/science/article/pii/S1936523324003930PMAIP1Breast cancerGlucose metabolismMulti-omicsTumor microenvironment
spellingShingle Yidong Zhang
Hang Xu
Xuedan Han
Qiyi Yu
Lufeng Zheng
Hua Xiao
PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
Translational Oncology
PMAIP1
Breast cancer
Glucose metabolism
Multi-omics
Tumor microenvironment
title PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
title_full PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
title_fullStr PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
title_full_unstemmed PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
title_short PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation
title_sort pmaip1 mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer integration of multi omics analysis and experimental validation
topic PMAIP1
Breast cancer
Glucose metabolism
Multi-omics
Tumor microenvironment
url http://www.sciencedirect.com/science/article/pii/S1936523324003930
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