Posted: Wednesday, May 24, 2023
Chinese investigators conducted a comprehensive study to explore the potential functions of cuproptosis—a type of cell death dependent on copper—in the tumor microenvironment of bladder cancer. Cuproptosis, which occurs through the combination of copper with lipoylated components in the tricarboxylic acid cycle, has been found to play a role in tumor progression and characterization of the tumor microenvironment in this type of genitourinary cancer. In an article published in Peerj, Zheng et al, of Guangdong Second Provincial General Hospital, Guangzhou, China, created a cuproptosis-related prognosis signature, which can stratify patients into high- and low-risk groups.
“The cuproptosis-related prognosis signature is a useful biomarker that can reflect the prognosis, tumor microenvironment characteristics, immunotherapeutic response, and chemotherapeutic drug susceptibility in bladder cancer patients,” concluded the investigators. “A tumor with a high concentration of lipoylated proteins is sensitive to cuproptosis, revealing that copper ionophore treatment may be an alternative treatment to these tumors that are resistant to traditional therapies.”
In their study, Zheng et al identified three subtypes of cuproptosis-associated molecules in 1,306 patients with bladder cancer, each with a distinct prognosis. These patients were from a combined data set including five gene-expression omnibus data sets and the IMvigor210 trial. A consensus clustering analysis was performed on 10 cupropotsis-related genes—ferredoxin 1, lipoic acid synthetase, lipoyltransferase 1, dihydrolipoamide dehydrogenase, dihydrolipoamide S-acetyltransferase, pyruvate dehydrogenase E1 subunit alpha 1, pyruvate dehydrogenase E1 subunit beta, metal regulatory transcription factor 1, glutaminase, and cyclin-dependent kinase inhibitor 2A. The correlation among the molecular subtypes and clinical features and prognoses was explored.
The investigators developed the cuproptosis-related prognosis signature. The researchers compared somatic mutations, tumor mutational burden, cuproptosis score, and IC50 values of chemotherapeutic agents between the low-risk and high-risk patients and identified characteristics of the tumor microenvironment in distinct risk groups.
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