Systematic analysis of the aberrances and functional implications of cuproptosis in cancer

Jiangbing Li; Boyan Li; Rongrong Zhao; Gang Li

doi:10.1016/j.isci.2023.106319

Systematic analysis of the aberrances and functional implications of cuproptosis in cancer

iScience. 2023 Mar 2;26(4):106319. doi: 10.1016/j.isci.2023.106319. eCollection 2023 Apr 21.

Authors

Jiangbing Li¹, Boyan Li^{2

3}, Rongrong Zhao^{2

3}, Gang Li^{2

3}

Affiliations

¹ Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021 Shandong, China.
² Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012 Shandong, China.
³ Shandong Key Laboratory of Brain Function Remodeling, Jinan, 250012 Shandong, China.

Abstract

Cuproptosis is a novel form of cell death driven by a copper-dependent proteotoxic stress response whose comprehensive landscape in tumors remains unclear. Here, we comprehensively characterized cuproptosis-related genes (CRGs) across 33 cancers using multi-omic data from The Cancer Genome Atlas (TCGA), showing complicated and diverse results in different cancers. We also explored the relationships between CRGs and cancer metabolic patterns, pathway activity, and tumor microenvironment (TME), suggesting that they played critical roles in tumor progression and TME cell infiltration. We further established the cuproptosis potential index (CPI) to reveal the functional roles of cuproptosis, and characterized multi-omic molecular features associated with cuproptosis. In clinical applications, we performed a combined analysis of the sensitivity of CRGs and CPI to drug response and immunotherapy. This study provides a rich resource for understanding cuproptosis, offering a broad molecular perspective for future functional and therapeutic studies of multiple cancer pathways mediated by cuproptosis.

Keywords: Cancer systems biology; Cell biology; Omics.