Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets
Abstract Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteog...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202401041 |
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| author | Ganfei Xu Juan Yu Jiacheng Lyu Mengna Zhan Jie Xu Minjing Huang Rui Zhao Yan Li Jiajun Zhu Jinwen Feng Subei Tan Peng Ran Zhenghua Su Xinhua Liu Jianyuan Zhao Hongwei Zhang Chen Xu Jun Chang Yingyong Hou Chen Ding |
| author_facet | Ganfei Xu Juan Yu Jiacheng Lyu Mengna Zhan Jie Xu Minjing Huang Rui Zhao Yan Li Jiajun Zhu Jinwen Feng Subei Tan Peng Ran Zhenghua Su Xinhua Liu Jianyuan Zhao Hongwei Zhang Chen Xu Jun Chang Yingyong Hou Chen Ding |
| author_sort | Ganfei Xu |
| collection | DOAJ |
| description | Abstract Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi‐step progression of BRDC, such as tumor protein P53 (TP53) mutation‐associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification‐associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T‐cell lymphoma invasion and metastasis 1, androgen receptor, and aldo‐keto reductase family 1 member C1 (TIAM1‐AR‐AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi‐omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages. |
| format | Article |
| id | doaj-art-2ee4698c97104a6fbe72eda9fa5770c2 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-2ee4698c97104a6fbe72eda9fa5770c22025-08-20T02:33:42ZengWileyAdvanced Science2198-38442024-12-011146n/an/a10.1002/advs.202401041Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic TargetsGanfei Xu0Juan Yu1Jiacheng Lyu2Mengna Zhan3Jie Xu4Minjing Huang5Rui Zhao6Yan Li7Jiajun Zhu8Jinwen Feng9Subei Tan10Peng Ran11Zhenghua Su12Xinhua Liu13Jianyuan Zhao14Hongwei Zhang15Chen Xu16Jun Chang17Yingyong Hou18Chen Ding19State Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaInstitute for Developmental and Regenerative Cardiovascular Medicine MOE‐Shanghai Key Laboratory of Children's Environmental Health Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200092 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaInstitute for Developmental and Regenerative Cardiovascular Medicine MOE‐Shanghai Key Laboratory of Children's Environmental Health Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200092 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaState Key Laboratory of Genetic Engineering School of Life Sciences Human Phenome Institute Department of Pathology Zhongshan Hospital, Fudan University Shanghai 200433 ChinaAbstract Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi‐step progression of BRDC, such as tumor protein P53 (TP53) mutation‐associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification‐associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T‐cell lymphoma invasion and metastasis 1, androgen receptor, and aldo‐keto reductase family 1 member C1 (TIAM1‐AR‐AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi‐omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.https://doi.org/10.1002/advs.202401041AKR1C1breast ductal carcinomaprogressionproteogenomicssterol hormone receptor |
| spellingShingle | Ganfei Xu Juan Yu Jiacheng Lyu Mengna Zhan Jie Xu Minjing Huang Rui Zhao Yan Li Jiajun Zhu Jinwen Feng Subei Tan Peng Ran Zhenghua Su Xinhua Liu Jianyuan Zhao Hongwei Zhang Chen Xu Jun Chang Yingyong Hou Chen Ding Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets Advanced Science AKR1C1 breast ductal carcinoma progression proteogenomics sterol hormone receptor |
| title | Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets |
| title_full | Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets |
| title_fullStr | Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets |
| title_full_unstemmed | Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets |
| title_short | Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets |
| title_sort | proteogenomic landscape of breast ductal carcinoma reveals tumor progression characteristics and therapeutic targets |
| topic | AKR1C1 breast ductal carcinoma progression proteogenomics sterol hormone receptor |
| url | https://doi.org/10.1002/advs.202401041 |
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