Multidimensional Proteomic Landscape Reveals Distinct Activated Pathways Between Human Brain Tumors.

in Advanced science (Weinheim, Baden-Wurttemberg, Germany) by Shuang Yang, Yongtao Zheng, Chengbin Zhou, Jun Yao, Guoquan Yan, Chengpin Shen, Siyuan Kong, Yueting Xiong, Qingfang Sun, Yuhao Sun, Huali Shen, Liuguan Bian, Kun Qian, Xiaohui Liu

TLDR

  • The study presents a comprehensive proteomic landscape of brain metastases and gliomas, identifying potential immunohistochemistry biomarkers, therapeutic targets, and non-invasive biomarkers for accurate diagnosis.
  • The findings highlight disparities between BrMs and gliomas in the PI3K-Akt signaling pathway and provide insights into the molecular pathophysiology of brain tumors.

Abstract

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.

Overview

  • The study explores the proteomic landscape of brain metastases (BrMs) and gliomas to understand their molecular pathophysiology at both tissue and plasma levels.
  • Tissue sample analysis reveals shared and distinct characteristics of brain tumors, highlighting disparities between BrMs and gliomas in the PI3K-Akt signaling pathway.
  • The study aims to identify potential immunohistochemistry (IHC) biomarkers and therapeutic targets for brain tumors, as well as non-invasive biomarkers for accurate diagnosis.

Comparative Analysis & Findings

  • The study identifies differentially activated upstream pathways of the PI3K-Akt signaling pathway in BrMs and gliomas, which have been scarcely discussed previously.
  • Novel proteins and phosphosites, such as NSUN2, TM9SF3, and PRKCG_S330, are detected, exhibiting a high correlation with reported clinical traits.
  • Tumor-specific altered phosphosites and glycosites on FN1 are highlighted as potential therapeutic targets.

Implications and Future Directions

  • The study provides a valuable resource for advancing precision medicine in cancer patients through targeted therapy and immunotherapy.
  • Future studies should validate the identified biomarkers and explore their potential in clinical practice.
  • The study's findings may lead to the development of novel diagnostic and therapeutic strategies for brain metastases and gliomas.
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