iProXProteomicsChen DingHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0004887000chend@fudan.edu.cnFudan UniversityiProXMulti-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.Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets.Xu Ganfei G, Yu Juan J, Lyu Jiacheng J, Zhan Mengna M, Xu Jie J, Huang Minjing M, Zhao Rui R, Li Yan Y, Zhu Jiajun J, Feng Jinwen J, Tan Subei S, Ran Peng P, Su Zhenghua Z, Liu Xinhua X, Zhao Jianyuan J, Zhang Hongwei H, Xu Chen C, Chang Jun J, Hou Yingyong Y, Ding Chen CfalseProteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic TargetsIn this study, we performed integrated multi-omics analyses using genomic (n = 79), transcriptomic (n = 42), proteomic (n = 224), and phosphoproteomic (n = 49) data collected from 224 samples from 168 patients with malignant and benign breast diseases. Our data revealed the characteristics of the linear multi-step progression of BRDC and provided a resource to explore the temporal order of a series of biological events in the progression of BRDC. In addition, we identified potential therapeutic agents, aspirin and dydrogesterone, that target AKR1C1 and demonstrated their inhibitory effect on tumor cells. In summary, our study helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.Fri Aug 02 00:00:00 GMT+01:00 2024PXD040750960639418072