Prognostic and immune correlation of IDO1 promoter methylation in breast cancer

Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the initiation and progression of breast cancer. DNA promoter methylation status has the potential to be used as a biomarker for predicting the response to immunotherapy. This study aimed to investigate the biological and clini...

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Main Authors: Shirong Ding, Ruozhu Yang, Jiahao Meng, Xinyu Guan, Yue Hong, Jiachi Xu, Limeng Qu, Jingfen Ji, Wenjun Yi, Qiongyan Zou, Qian Long
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-79149-w
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author Shirong Ding
Ruozhu Yang
Jiahao Meng
Xinyu Guan
Yue Hong
Jiachi Xu
Limeng Qu
Jingfen Ji
Wenjun Yi
Qiongyan Zou
Qian Long
author_facet Shirong Ding
Ruozhu Yang
Jiahao Meng
Xinyu Guan
Yue Hong
Jiachi Xu
Limeng Qu
Jingfen Ji
Wenjun Yi
Qiongyan Zou
Qian Long
author_sort Shirong Ding
collection DOAJ
description Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the initiation and progression of breast cancer. DNA promoter methylation status has the potential to be used as a biomarker for predicting the response to immunotherapy. This study aimed to investigate the biological and clinical significance of IDO1 promoter methylation in breast cancer. We analyzed IDO1 promoter methylation and its relationship with survival, patient prognosis, immune cell infiltration, immune-related pathways, and the expression of key immunomodulators via bioinformatics methods in The Cancer Genome Atlas (TCGA) breast cancer cohort (779 samples). Furthermore, the IDO1 promoter methylation status and expression of the IDO1 gene in the basal subtype of breast cancer were investigated in vitro via a methylation-specific PCR (MSP) assay and quantitative polymerase chain reaction (qPCR). The IDO1 promoter was significantly hypomethylated in the basal subtype of breast cancer tissues compared with normal adjacent tissues, and this effect was correlated with high expression of IDO1, resulting in abundant immune cell infiltration, activation of immune-related pathways, and upregulation of key immunomodulators. The influence of IDO1 promoter hypomethylation on the prognosis of patients with breast cancer was also investigated. The promoter hypomethylation of IDO1 in the basal subtype of breast cancer and its correlation with high expression of IDO1 were also investigated in vitro. Our results showed that IDO1 promoter methylation is vital for regulating its expression, which leads to the development of a tumor microenvironment in breast cancer. IDO1 promoter methylation and expression are associated with prognosis, immune cell infiltration, immune-related pathways, and immunomodulator expression in breast cancer. Our findings provide evidence for the validation of IDO1 promoter methylation as a promising biomarker to predict responses to immune checkpoint inhibitors in patients with breast cancer.
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spelling doaj-art-9950e7b80f2d4d52be9e7b914f1f83fe2024-11-17T12:23:21ZengNature PortfolioScientific Reports2045-23222024-11-0114111610.1038/s41598-024-79149-wPrognostic and immune correlation of IDO1 promoter methylation in breast cancerShirong Ding0Ruozhu Yang1Jiahao Meng2Xinyu Guan3Yue Hong4Jiachi Xu5Limeng Qu6Jingfen Ji7Wenjun Yi8Qiongyan Zou9Qian Long10Department of Oncology, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of General Surgery, the Second Xiangya Hospital of Central South UniversityAbstract Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the initiation and progression of breast cancer. DNA promoter methylation status has the potential to be used as a biomarker for predicting the response to immunotherapy. This study aimed to investigate the biological and clinical significance of IDO1 promoter methylation in breast cancer. We analyzed IDO1 promoter methylation and its relationship with survival, patient prognosis, immune cell infiltration, immune-related pathways, and the expression of key immunomodulators via bioinformatics methods in The Cancer Genome Atlas (TCGA) breast cancer cohort (779 samples). Furthermore, the IDO1 promoter methylation status and expression of the IDO1 gene in the basal subtype of breast cancer were investigated in vitro via a methylation-specific PCR (MSP) assay and quantitative polymerase chain reaction (qPCR). The IDO1 promoter was significantly hypomethylated in the basal subtype of breast cancer tissues compared with normal adjacent tissues, and this effect was correlated with high expression of IDO1, resulting in abundant immune cell infiltration, activation of immune-related pathways, and upregulation of key immunomodulators. The influence of IDO1 promoter hypomethylation on the prognosis of patients with breast cancer was also investigated. The promoter hypomethylation of IDO1 in the basal subtype of breast cancer and its correlation with high expression of IDO1 were also investigated in vitro. Our results showed that IDO1 promoter methylation is vital for regulating its expression, which leads to the development of a tumor microenvironment in breast cancer. IDO1 promoter methylation and expression are associated with prognosis, immune cell infiltration, immune-related pathways, and immunomodulator expression in breast cancer. Our findings provide evidence for the validation of IDO1 promoter methylation as a promising biomarker to predict responses to immune checkpoint inhibitors in patients with breast cancer.https://doi.org/10.1038/s41598-024-79149-wDNA methylationEpigeneticsBiomarkerIDO1Breast cancerTumor immune microenvironment
spellingShingle Shirong Ding
Ruozhu Yang
Jiahao Meng
Xinyu Guan
Yue Hong
Jiachi Xu
Limeng Qu
Jingfen Ji
Wenjun Yi
Qiongyan Zou
Qian Long
Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
Scientific Reports
DNA methylation
Epigenetics
Biomarker
IDO1
Breast cancer
Tumor immune microenvironment
title Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
title_full Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
title_fullStr Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
title_full_unstemmed Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
title_short Prognostic and immune correlation of IDO1 promoter methylation in breast cancer
title_sort prognostic and immune correlation of ido1 promoter methylation in breast cancer
topic DNA methylation
Epigenetics
Biomarker
IDO1
Breast cancer
Tumor immune microenvironment
url https://doi.org/10.1038/s41598-024-79149-w
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