Yang Shuang, Zheng Yongtao, Zhou Chengbin, Yao Jun, Yan Guoquan, Shen Chengpin, Kong Siyuan, Xiong Yueting, Sun Qingfang, Sun Yuhao, Shen Huali, Bian Liuguan, Qian Kun, Liu Xiaohui
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200241, P. R. China.
Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, P. R. China.
Adv Sci (Weinh). 2025 Feb;12(7):e2410142. doi: 10.1002/advs.202410142. Epub 2024 Dec 24.
Brain metastases (BrMs) and gliomas are two typical human brain tumors with high incidence of mortalities and distinct clinical challenges, yet the understanding of these two types of tumors remains incomplete. Here, a multidimensional proteomic landscape of BrMs and gliomas to infer tumor-specific molecular pathophysiology at both tissue and plasma levels is presented. Tissue sample analysis reveals both shared and distinct characteristics of brain tumors, highlighting significant disparities between BrMs and gliomas with differentially activated upstream pathways of the PI3K-Akt signaling pathway that have been scarcely discussed previously. Novel proteins and phosphosites such as NSUN2, TM9SF3, and PRKCG_S330 are also detected, exhibiting a high correlation with reported clinical traits, which may serve as potential immunohistochemistry (IHC) biomarkers. Moreover, tumor-specific altered phosphosites and glycosites on FN1 are highlighted as potential therapeutic targets. Further validation of 110 potential noninvasive biomarkers yields three biomarker panels comprising a total of 19 biomarkers (including DES, VWF, and COL1A1) for accurate discrimination of two types of brain tumors and normal controls. In summary, this is a full-scale dataset of two typical human brain tumors, which serves as a valuable resource for advancing precision medicine in cancer patients through targeted therapy and immunotherapy.
脑转移瘤（BrMs）和胶质瘤是两种典型的人类脑肿瘤，死亡率高且面临独特的临床挑战，但对这两种肿瘤的了解仍不完整。在此，展示了一个脑转移瘤和胶质瘤的多维蛋白质组图谱，以推断组织和血浆水平上肿瘤特异性的分子病理生理学。组织样本分析揭示了脑肿瘤的共同特征和不同特征，突出了脑转移瘤和胶质瘤之间的显著差异，其中PI3K-Akt信号通路的上游途径激活不同，而此前对此几乎没有讨论过。还检测到了诸如NSUN2、TM9SF3和PRKCG_S330等新蛋白和磷酸化位点，它们与已报道的临床特征高度相关，可能作为潜在的免疫组织化学（IHC）生物标志物。此外，纤连蛋白1（FN1）上肿瘤特异性改变的磷酸化位点和糖基化位点被突出显示为潜在的治疗靶点。对110种潜在的非侵入性生物标志物的进一步验证产生了三个生物标志物组，共包含19种生物标志物（包括DES、VWF和COL1A1），用于准确区分两种类型的脑肿瘤和正常对照。总之，这是一个两种典型人类脑肿瘤的全面数据集，通过靶向治疗和免疫治疗，为推进癌症患者的精准医学提供了宝贵资源。
