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Ferroptosis Gene Signature Predicts CRC Prognosis

May, 05, 2024 | Colorectal Cancer, Gastrointestinal Cancer

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic value of ferroptosis-related genes GPX3, CDKN2A, and SLC7A11 in CRC.
  • Researchers noticed that the 3-gene risk score signature and prognostic nomogram effectively predict outcomes in patients with CRC; further investigation is ongoing.

Colorectal cancer (CRC) has a high morbidity and mortality. Ferroptosis is a phenomenon in which metabolism and cell death are closely related. The role of ferroptosis-related genes in the progression of CRC is still not clear.

Ruibin Liu and the team aimed to screen and validate the ferroptosis-related genes that could determine the prevalence, risk, and prognosis of patients with CRC.

They performed an inclusive analysis by firstly screening differentially expressed ferroptosis-related genes using The Cancer Genome Atlas (TCGA) database. These genes were then used to construct a risk-score model employing the least absolute shrinkage and selection operator (LASSO) regression algorithm.

The function and prognosis of the ferroptosis-related genes were confirmed through multi-omics analysis. Gene expression results were validated using publicly available databases and qPCR. Additionally, researchers used publicly available data and ferroptosis-related genes to construct a prognostic prediction nomogram.

About 24 differentially expressed genes associated with ferroptosis were screened in this study. A three-gene risk score model was then established based on these 24 genes, and GPX3, CDKN2A, and SLC7A11 were selected. The significant prognostic value of this novel three-gene signature was also assessed. Furthermore, researchers conducted RT-qPCR analysis on cell lines and tissues and validated the high expression of CDKN2A and GPX3 and low expression of SLC7A11 in CRC cells. The observed mRNA expression of GPX3, CDKN2A, and SLC7A11 was consistent with the predicted outcomes.

Additionally, 8 variables, including selected ferroptosis-related genes, were included to establish the prognostic prediction nomogram for patients with CRC. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations. Also, the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram.

The study concluded that the novel ferroptosis-related three-gene risk score signature and prognostic prediction nomogram are effective tools for predicting outcomes in patients with CRC. Additionally, the ferroptosis-related genes GPX3, CDKN2A, and SLC7A11 were validated as potential biomarkers for CRC, providing valuable insights for future research and clinical applications.

This study was sponsored by the National Natural Science Cultivation Foundation of China of Liaoning Cancer Hospital, the Doctoral Start-up Foundation of Liaoning Province and “5310” Talent Strategy Project Funding Plan of Liaoning Cancer Hospital & Institute.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/38774759/

Liu R, Wang Y, Bu J, et al. (2024). “Construction and Validation of Novel Ferroptosis-related Risk Score Signature and Prognostic Prediction Nomogram for Patients with Colorectal Cancer.” Int J Med Sci. 2024 Apr 22;21(6):1103-1116. doi: 10.7150/ijms.91446. PMID: 38774759; PMCID: PMC11103399.

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