Is hypermethylation of SOX1 gene an independent prognostic marker in surgically resected non-small cell lung cancer?
Milica Kontic1, Dragana Jovanovic1, Izidor Kern2, Heather H Nelson3, Svetlana Bojic4, Miodrag Ognjanovic5, SImona Ognjanovic6
1 Clinic for Pulmonology, Clinical Center of Serbia; Department of Internal Medicine – Pulmonology, School of Medicine, University of Belgrade, Belgrade, Serbia
2 Department for Pathology, The University Clinic of Pulmonary and Allergic Diseases Golnik, Golnik, Slovenia
3 Division of Epidemiology and Community Health, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
4 Institute for Medical Statistics and Informatics, School of Medicine, University of Belgrade, Belgrade, Serbia
5 International Organization for Cancer Prevention and Research, Belgrade, Serbia
6 Mayo Clinic, Mayo Graduate School, Rochester, New York, USA
Clinic for Pulmonology, Clinical Center of Serbia, Belgrade, Serbia
Source of Support: None, Conflict of Interest: None
Background: Promoter hypermethylation of tumor suppressor genes presents promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the association between the promoter hypermethylation of multiple genes and 5-year survival rate in patients with Non-small cell lung cancer (NSCLC).
Materials and Methods: Primary tumor samples (n = 65), corresponding nonmalignant lung tissues (n = 65), and circulating blood were obtained from NSCLC patients who underwent curative surgery. Promoter methylation status in seven genes (RASSF1A, CDH13, MGMT, ESR1, DAPK, SOX1, and HOXA9) was quantified by using bisulfite pyrosequencing. Five-year survival data were obtained by a clinician. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival.
Results: The 5-year survival of the patients with SOX1 aberrant tumor methylation was found to be statistically significantly shorter than for those patients without aberrant tumor methylation (P = 0.01). This effect was independent of TNM stage. No significant survival differences were associated with aberrant methylation in other genes tested in either of the two tissue types.
Conclusion: Our study shows that SOX1 promoter hypermethylation in NSCLC tumors is significantly associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC.