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Open Search-Based Proteomics Reveals Widespread Tryptophan Modifications Associated with Hypoxia in Lung Cancer
Jinfeng Chen1, Lei Zhang1, Zhao Sun2
1Clinical Systems Biology Key Laboratories of Henan, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China.
Oxidative Medicine and Cellular Longevity
|May 10, 2022
Summary
Researchers identified novel tryptophan variants in nonsmall cell lung cancer (NSCLC) patients using proteomics. These variants, particularly oxidation changes in GAPDH and HBB, reveal insights into cancer
Area of Science:
- Proteomics and Cancer Biology
- Biochemistry and Molecular Biology
Background:
- Tryptophan residues are crucial for protein structure and function due to their hydrophobic nature.
- The indole ring of tryptophan is susceptible to electrophilic attack, making its modifications detectable.
- Nonsmall cell lung cancer (NSCLC) involves complex molecular alterations, including potential protein modifications.
Purpose of the Study:
- To systematically identify and characterize sequence variations at tryptophan residues (tryptophan variants) in the proteome of NSCLC patients.
- To explore the role of tryptophan modifications in the context of cancer biology and potential biomarker discovery.
Main Methods:
- Utilized shotgun proteomics combined with a modified open search algorithm for comprehensive proteome analysis.
- Analyzed protein samples from NSCLC patients to identify and quantify tryptophan variants.
- Validated findings using an independent cohort of lung adenocarcinoma samples.
Main Results:
- Identified 25 tryptophan variants across 858 proteins in NSCLC patients.
- Discovered 15 newly annotated and 4 unknown tryptophan variants, many linked to oxidation pathways.
- Observed specific oxidation changes in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and hemoglobin (HBB) in NSCLC tissues.
- Confirmed findings in lung adenocarcinoma samples, suggesting a detoxification mechanism against tumor glycolysis and hypoxia.
Conclusions:
- Tryptophan oxidation plays a significant role in regulating the redox balance within cancer cells.
- The identified tryptophan variants, especially oxidation patterns, show potential as prognostic biomarkers for NSCLC.
- Developed an efficient proteomic approach for large-scale exploration of tryptophan variants.
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