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Published on: March 15, 2024
Identification and validation of m6A-associated ferroptosis genes in renal clear cell carcinoma
Shuo Pang1,2, Shuo Zhao1, Yuxi Dongye1,2
1Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Abstract:
Urinary cancer is synonymous with clear cell renal cell carcinoma (ccRCC). Unfortunately, existing treatments for this illness are ineffective and unpromising. Finding novel ccRCC biomarkers is crucial to creating successful treatments. The Cancer Genome Atlas provided clear cell renal cell carcinoma transcriptome data. Functional enrichment analysis was performed on ccRCC and control samples' differentially expressed N6-methyladenosine RNA methylation and ferroptosis-related genes (DEMFRGs). Machine learning was used to find and model ccRCC patients' predicted genes. A nomogram was created for clear cell renal cell carcinoma patients. Prognostic genes were enriched. We examined patients' immune profiles by risk score. Our prognostic genes predicted ccRCC treatment drugs. We found 37 DEMFRGs by comparing 1913 differentially expressed ccRCC genes to 202 m6A RNA methylation FRGs. Functional enrichment analysis showed that hypoxia-induced cell death and metabolism pathways were the most differentially expressed methylation functional regulating genes. Five prognostic genes were found by machine learning: TRIB3, CHAC1, NNMT, EGFR, and SLC1A4. An advanced renal cell carcinoma nomogram with age and risk score accurately predicted the outcome. These five prognostic genes were linked to various cancers. Immunological cell number and checkpoint expression differed between high- and low-risk groups. The risk model successfully predicted immunotherapy outcome, showing high-risk individuals had poor results. NIACIN, TAE-684, ROCILETINIB, and others treat ccRCC. We found ccRCC prognostic genes that work. This discovery may lead to new ccRCC treatments.
Insights
Novel biomarkers for clear cell renal cell carcinoma (ccRCC) were identified using gene expression data. These biomarkers can predict patient outcomes and potential drug treatments for this urinary cancer.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant urinary cancer with limited effective treatments.
- Identifying novel biomarkers is critical for developing targeted therapies and improving patient outcomes.
Purpose of the Study:
- To identify novel prognostic biomarkers for clear cell renal cell carcinoma (ccRCC).
- To develop a predictive model for ccRCC patient outcomes and response to immunotherapy.
- To explore potential therapeutic targets for ccRCC treatment.
Main Methods:
- Differential gene expression analysis of ccRCC and control samples.
- Functional enrichment analysis of differentially expressed N6-methyladenosine RNA methylation and ferroptosis-related genes (DEMFRGs).
- Machine learning algorithms to identify and model prognostic genes, followed by nomogram construction.
Main Results:
- Identified 37 DEMFRGs, with hypoxia-induced cell death and metabolism pathways being significantly enriched.
- Discovered five key prognostic genes: TRIB3, CHAC1, NNMT, EGFR, and SLC1A4.
- Developed a nomogram that accurately predicts ccRCC patient outcomes and immunotherapy response, with high-risk groups showing poorer results.
Conclusions:
- The identified prognostic genes are linked to various cancers and can predict ccRCC treatment efficacy.
- The developed risk model shows potential for predicting immunotherapy outcomes in ccRCC patients.
- This research offers promising new biomarkers and potential therapeutic strategies for clear cell renal cell carcinoma.
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