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Translation initiation factor eIF-4G is immunogenic, overexpressed, and amplified in patients with squamous cell lung
C Bauer1, I Diesinger, N Brass
1Department of Human Genetics, Medical School, University of Saarland, 66421 Homburg/Saar, Germany.
Background:
Recently, the authors reported identification and cloning of several novel immunogenic antigens in squamous cell lung carcinoma. Of 14 corresponding genes, 9 mapped in an amplified chromosomal region with the gene for eIF-4G that was amplified most frequently.
Methods:
Recombinant eIF-4G was expressed in E. coli and screened with sera from patients with squamous cell carcinoma of the lung and of the head and neck. Protein extracts from squamous cell carcinoma tissues were analyzed for eIF-4G expression by Western blot analysis. Mutation analysis was performed using an automatic DNA sequencer.
Results:
The authors screened a spectrum of 33 heterologous sera from lung carcinoma patients and detected antibodies against eIF-4G in 5 of these sera (15%). They found no immune response to eIF-4G in 17 sera from squamous cell carcinoma tissues derived from the head and neck. In addition, no antibodies were found to eIF-4G in a group of 17 control sera from individuals without known tumor formation. Sequence analysis of the eIF-4G gave no indication of mutations. To analyze the expression of eIF-4G, a monoclonal antibody was used. Western blot analysis clearly showed overexpression in the tumor tissue compared with the corresponding normal lung tissues.
Conclusions:
The translation initiation factor eIF-4G is the first protein in which the gene shows amplification, has increased expression in a human tumor, and induces an immune response in patients. eIF-4G lends itself as a marker for the diagnosis of and possibly as a future therapeutic target in patients with squamous cell lung carcinoma.
Insights
Antibodies against eukaryotic initiation factor 4G (eIF-4G) were detected in lung cancer patients. This protein, overexpressed in tumors, shows potential as a diagnostic marker and therapeutic target for squamous cell lung carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Novel immunogenic antigens in squamous cell lung carcinoma were previously identified.
- Nine of 14 corresponding genes mapped to an amplified chromosomal region, including the eukaryotic initiation factor 4G (eIF-4G) gene, which was most frequently amplified.
Purpose of the Study:
- To investigate the immunogenicity and expression of eIF-4G in squamous cell lung carcinoma.
- To determine if eIF-4G could serve as a diagnostic marker or therapeutic target.
Main Methods:
- Recombinant eIF-4G was expressed and screened with patient sera.
- Western blot analysis was used to assess eIF-4G expression in tumor tissues.
- Mutation analysis was performed on the eIF-4G gene.
Main Results:
- Antibodies against eIF-4G were detected in 15% of lung carcinoma patients' sera.
- No immune response was observed in head and neck squamous cell carcinoma patients or healthy controls.
- Overexpression of eIF-4G was confirmed in tumor tissues compared to normal lung tissues.
- No mutations were found in the eIF-4G gene sequence.
Conclusions:
- eIF-4G is the first identified protein with gene amplification, increased tumor expression, and induction of an immune response in cancer patients.
- eIF-4G shows promise as a diagnostic marker for squamous cell lung carcinoma.
- eIF-4G may represent a future therapeutic target for squamous cell lung carcinoma.