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S. Ognjanovic
Author of
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-005 - Hypermethylation of the RASSF1A and SOX1 Genes in Tumor DNA Predicts Unfavorable Overall Survival in Surgically Resected NSCLC Patients (ID 8741)
09:30 - 09:30 | Author(s): S. Ognjanovic
- Abstract
Background:
The possibility of detection of tumor suppressor genes methylation in tumor DNA of NSCLC patients and the lack of methylation in healthy individuals makes this epigenetic alternation a potential diagnostic and prognostic marker of lung neoplastic processes. The aims of our study was to evaluate the promoter methylation of 7 genes in tumor DNA of NSCLC patients, matching nonmalignant lung tissue and blood samples to test weather these changes are lung cancer specific. We also wanted to investigate usefulness of this test for predicting the lung cancer course.
Method:
Genes methylation status was evaluated in DNA isolated from tumor, matching nonmalignant lung tissue and peripheral blood samples from 65 NSCLC patients treated with curative resectional surgery. Hypermethylation status was quantified at multiple CpG sites within each promoter in multiple genes - CDH13, MGMT, ESR1, SOX1, RASSF1A, HOXA9, and DAPK by pyrosequencing. Percent methylation for each CpG as well as average methylation across CpG’s was calculated for each promoter using PyroMark software (Qiagen).
Result:
Aberrant methylation in SOX1 and RASSF1A genes in tumor tissues were associated with inferior survival in surgically resected NSCLC patients. This effect was independent of TNM stage, which was also a predictor of survival. Methylation in tumors was significantly higher than in normal lung for SOX1, DAPK, RASSF1A, HOXA9 and CDH13. However, these changes could not be detected in patients’ blood samples, indicating a low feasibility of detecting lung cancer by analyzing these genes in a blood-based test.
Conclusion:
Hypermethylation of SOX1 and RASSF1A genes in NSCLC correlates with poor prognosis of patients. It may serve as novel epigenetic-based diagnostic biomarkers with further clinical impact for risk stratification of NSCLC patients. Our results also show that elevated methylation levels observed in genes SOX1, RASSF1A, HOXA9, CDH13 and DAPK in NSCLC were cancer-specific. We confirm that hypermethylation of these genes plays a role in NSCLC pathogenesis. However, the lack of reflection of these methylation changes in patients blood indicate their poorly suitability for a screening test.
