Characterization of ROS Metabolic Equilibrium Reclassifies Pan-Cancer Samples and Guides Pathway Targeting Therapy

Frontiers in Oncology
Shuai ShenAnhua Wu

Abstract

Background: Abnormal redox equilibrium is a major contributor to tumor malignancy and treatment resistance. Understanding reactive oxygen species (ROS) metabolism is a key to clarify the tumor redox status. However, we have limited methods to evaluate ROS in tumor tissues and little knowledge on ROS metabolism across human cancers. Methods: The Cancer Genome Atlas multi-omics data across 22 cancer types and the Genomics of Drug Sensitivity in Cancer data were analyzed in this study. Cell viability testing and xenograft model were used to validate the role of ROS modulation in regulating treatment efficacy. Results: ROS indexes reflecting ROS metabolic balance in five dimensions were developed and verified. Based on the ROS indexes, we conducted ROS metabolic landscape across 22 cancer types and found that ROS metabolism played various roles in different cancer types. Tumor samples were classified into eight ROS clusters with distinct clinical and multi-omics features, which was independent of their histological origin. We established a ROS-based drug efficacy evaluation network and experimentally validated the predicted effects, suggesting that modulating ROS metabolism improves treatment sensitivity and expands drug applicatio...Continue Reading

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Methods Mentioned

BETA
protein assay
Xenograft

Clinical Trials Mentioned

NCT00512798

Software Mentioned

GSVA
Graph Pad
SNE
Cytoscape
Amigo2
SPSS
Xena
R package
R
pheatmap R package

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