Qian Liujia, Zhu Jianqing, Xue Zhangzhi, Zhou Yan, Xiang Nan, Xu Hong, Sun Rui, Gong Wangang, Cai Xue, Sun Lu, Ge Weigang, Liu Yufeng, Su Ying, Lin Wangmin, Zhan Yuecheng, Wang Junjian, Song Shuang, Yi Xiao, Ni Maowei, Zhu Yi, Hua Yuejin, Zheng Zhiguo, Guo Tiannan
School of Medicine, Westlake University, Hangzhou, Zhejiang Province, China.
Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang Province, China.
Nat Commun. 2024 Jul 31;15(1):6462. doi: 10.1038/s41467-024-50786-z.
Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.
上皮性卵巢癌（EOC）是一种致命疾病，其诊断生物标志物和治疗靶点有限。在此，我们对813例不同组织学类型和治疗方案的患者的卵巢组织和血浆样本进行了全面的蛋白质组分析，涵盖了10715种蛋白质的表达情况。我们在组织标本中鉴定出8种与肿瘤恶性程度相关的蛋白质，这些蛋白质在血浆中进一步被验证为潜在的循环生物标志物。针对12种组织蛋白和7种血液蛋白开发了靶向蛋白质组学检测方法，并构建了机器学习模型来预测一年复发情况，这些在一个独立队列中得到了验证。这些发现有助于理解EOC的发病机制，并为该疾病的早期检测和监测提供潜在的生物标志物。此外，通过将突变分析与蛋白质组数据相结合，我们在复发性耐药肿瘤中鉴定出多种与DNA损伤相关的蛋白质，揭示了治疗耐药的分子机制。本研究提供了EOC的多组织学类型蛋白质组图谱，推进了我们对改善诊断和治疗策略的认识。
