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Systematic Identification of Multi Omics-based Biomarkers in KEAP1 Mutated TCGA Lung Adenocarcinoma
Akhileshwar Namani1, Zhaohong Zheng2, Xiu Jun Wang2
1Department of Thoracic Surgery and Department of Biochemistry of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China.
Abstract:
Mutations in KEAP1 and/or NRF2 genes have been identified across many cancers and the dysregulation of the NRF2 pathway due to these mutations leads to drug and radioresistance in several cancers. Identification of biomarkers associated with these mutations allows the researchers and clinicians to identify the personalized medicine and quicker diagnosis. In this current study, we carried out an integrated, multi-omics, multi-database analysis of exome, transcriptomics data's of KEAP1 mutated TCGA- Lung adenocarcinoma (LUAD) patients against non-mutated counterparts. Finally, we discovered the gene signature associated with KEAP1 mutations, prognostic genes which were highly correlated with the upregulation of the NRF2 pathway in the KEAP1 mutated LUAD patients. Our finding might be useful to identify the early diagnosis of KEAP1 mutated LUAD patients.
Insights
KEAP1 mutations in lung adenocarcinoma activate the NRF2 pathway, leading to drug resistance. This study identifies a gene signature for early diagnosis and personalized medicine in KEAP1-mutated LUAD patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in Kelch-like ECH-associated protein 1 (KEAP1) and Nuclear factor erythroid 2-related factor 2 (NRF2) genes are prevalent in various cancers.
- KEAP1/NRF2 pathway dysregulation contributes to drug and radioresistance in multiple cancer types.
- Biomarkers for these mutations aid in personalized medicine and expedited cancer diagnosis.
Purpose of the Study:
- To identify a gene signature associated with KEAP1 mutations in lung adenocarcinoma (LUAD).
- To discover prognostic genes linked to NRF2 pathway upregulation in KEAP1-mutated LUAD.
- To explore potential biomarkers for early diagnosis of KEAP1-mutated LUAD.
Main Methods:
- Integrated analysis of multi-omics data, including exome and transcriptomics.
- Utilized The Cancer Genome Atlas (TCGA) database for patient data.
- Compared KEAP1-mutated LUAD patients with non-mutated counterparts.
Main Results:
- Identified a specific gene signature associated with KEAP1 mutations in LUAD.
- Discovered prognostic genes highly correlated with NRF2 pathway upregulation in KEAP1-mutated LUAD.
- Established a link between KEAP1 mutations, NRF2 pathway activity, and patient prognosis.
Conclusions:
- The identified gene signature may serve as a valuable tool for early diagnosis of KEAP1-mutated LUAD.
- Findings support the role of the NRF2 pathway in resistance mechanisms in LUAD.
- This research provides a foundation for developing targeted therapies and personalized treatment strategies for LUAD patients with KEAP1 mutations.
