Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes
Abstract The individual variation of carcinogenesis and drug response is influenced by the absorption, distribution, metabolism, and excretion (ADME) of drugs. The utilization of signatures derived from ADME-related genes holds potential for predicting prognosis and treatment response across diverse...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-09-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-72635-1 |
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| author | Zhixuan Wu Yangyang Guo Liangchen Qu Xiaowu Wang Hewei Zhang |
| author_facet | Zhixuan Wu Yangyang Guo Liangchen Qu Xiaowu Wang Hewei Zhang |
| author_sort | Zhixuan Wu |
| collection | DOAJ |
| description | Abstract The individual variation of carcinogenesis and drug response is influenced by the absorption, distribution, metabolism, and excretion (ADME) of drugs. The utilization of signatures derived from ADME-related genes holds potential for predicting prognosis and treatment response across diverse cancer types. Further investigation is required to completely understand the role of ADME-associated genes in breast cancer. A signature was constructed through the application of a least absolute shrinkage and selection operator regression model, employing prognostic differentially expressed genes found in both cancer tissue and normal tissue. To assess the robustness of the signature, verification analyses were carried out. RT-qPCR was utilized for the validation of gene expression related to risk. Subsequently, a nomogram was developed to enhance the clinical utility of our prognostic tool. The ADME signature, comprising four genes, was established and exhibited a robust association with the prognoses of individuals diagnosed with breast cancer. The nomogram was created by fusing the clinicopathological characteristics with the ADME signature. The ADME signature demonstrated remarkable superiority when compared to the performance of the other individual predictors. Additionally, the analysis of the immune microenvironment revealed that the ImmuneScores of the low-risk group were elevated. The variation in both the infiltration of immune cells and the expression of immune-related genes in the tissues differed among the two groups. For patients with breast cancer, the utilization of ADME signatures as biomarkers presents a significant reference point for prognosis and individualized treatment strategies. |
| format | Article |
| id | doaj-art-99c2d22a819a403ba5901ce21b6543e2 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-99c2d22a819a403ba5901ce21b6543e22025-01-05T12:25:44ZengNature PortfolioScientific Reports2045-23222024-09-0114111410.1038/s41598-024-72635-1Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genesZhixuan Wu0Yangyang Guo1Liangchen Qu2Xiaowu Wang3Hewei Zhang4 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical UniversityEmergency Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical UniversityDepartment of Burns and Skin Repair Surgery, The Third Affiliated Hospital of Wenzhou Medical UniversityThe Dingli Clinical College of Wenzhou Medical UniversityAbstract The individual variation of carcinogenesis and drug response is influenced by the absorption, distribution, metabolism, and excretion (ADME) of drugs. The utilization of signatures derived from ADME-related genes holds potential for predicting prognosis and treatment response across diverse cancer types. Further investigation is required to completely understand the role of ADME-associated genes in breast cancer. A signature was constructed through the application of a least absolute shrinkage and selection operator regression model, employing prognostic differentially expressed genes found in both cancer tissue and normal tissue. To assess the robustness of the signature, verification analyses were carried out. RT-qPCR was utilized for the validation of gene expression related to risk. Subsequently, a nomogram was developed to enhance the clinical utility of our prognostic tool. The ADME signature, comprising four genes, was established and exhibited a robust association with the prognoses of individuals diagnosed with breast cancer. The nomogram was created by fusing the clinicopathological characteristics with the ADME signature. The ADME signature demonstrated remarkable superiority when compared to the performance of the other individual predictors. Additionally, the analysis of the immune microenvironment revealed that the ImmuneScores of the low-risk group were elevated. The variation in both the infiltration of immune cells and the expression of immune-related genes in the tissues differed among the two groups. For patients with breast cancer, the utilization of ADME signatures as biomarkers presents a significant reference point for prognosis and individualized treatment strategies.https://doi.org/10.1038/s41598-024-72635-1ADMEBreast cancerImmune microenvironmentImmunotherapyPrognosis |
| spellingShingle | Zhixuan Wu Yangyang Guo Liangchen Qu Xiaowu Wang Hewei Zhang Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes Scientific Reports ADME Breast cancer Immune microenvironment Immunotherapy Prognosis |
| title | Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes |
| title_full | Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes |
| title_fullStr | Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes |
| title_full_unstemmed | Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes |
| title_short | Development and validation of a prognostic signature of breast cancer based on drug absorption, distribution, metabolism and excretion (ADME)-related genes |
| title_sort | development and validation of a prognostic signature of breast cancer based on drug absorption distribution metabolism and excretion adme related genes |
| topic | ADME Breast cancer Immune microenvironment Immunotherapy Prognosis |
| url | https://doi.org/10.1038/s41598-024-72635-1 |
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