Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Cancer Cell. 2023 Sep 11;41(9):1586-1605.e15. doi: 10.1016/j.ccell.2023.07.007. Epub 2023 Aug 10.
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.
我们使用 10 种不同的组学平台对包含 138 个肿瘤和 20 个富集正常组织的前瞻性子宫内膜癌 (EC) 队列进行了特征描述。两种肽的靶向定量可以预测抗原加工和呈递机制的活性，并可能为免疫治疗患者的选择提供信息。在患者和细胞系中，MYC 活性与二甲双胍治疗之间的关联分析表明，二甲双胍治疗在 MYC 活性升高的非糖尿病患者中可能具有潜在作用。PIK3R1 框内缺失与 AKT 磷酸化升高和对 AKT 抑制剂的敏感性增加有关。CTNNB1 热点突变集中在介导 pS45 诱导的 β-连环蛋白降解的磷酸化位点附近，这可能使 Wnt-FZD 拮抗剂无效。深度学习可以从组织病理学图像中准确预测 EC 亚型和突变，这可能有助于快速诊断。总的来说，这项研究确定了分子和影像学标志物，可以进一步研究以指导患者分层，从而更精确地治疗 EC。
