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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Nature Portfolio
2024-11-01
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| 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. |
| format | Article |
| id | doaj-art-9950e7b80f2d4d52be9e7b914f1f83fe |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| 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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