Methylated DLX4 Predicts Response to Pathologic Stage I Non-Small Cell Lung Cancer Resection

作者：Harada Hiroaki^*; Miyamoto Kazuaki; Yamashita Yoshinori; Taniyama Kiyomi; Ohdan Hideki; Okada Morihito

来源：Annals of Thoracic Surgery, 2015, 99(5): 1746-1754.

DOI：10.1016/j.athoracsur.2014.12.058

Background. Surgery with curative intent is the standard treatment for patients with stage I non-small cell lung cancer (NSCLC). Even after curative resection, however, many patients have recurrent disease. Thus, there is a need to identify molecular biomarkers for the biological characteristics and prognosis of tumors.
Methods. Methylation-specific polymerase chain reaction analysis was performed for the distal-less homeobox 4 (DLX4) gene in cancer tissues from 109 patients who underwent curative resection for pathologic stage I NSCLC from June 2005 to November 2011. We investigated possible correlations between DLX4 methylation status and disease outcome.
Results. Methylated DLX4 was detected in 54 of 109 patients (49.5%). No significant relationship between DLX4 methylation status and clinicopathologic features was found. Multivariate logistic regression analysis revealed that DLX4 methylation was an independent risk factor for recurrence (p < 0.0001). Patients with DLX4 methylation showed significantly poorer recurrence-free, cancer-specific, and overall survival than patients without DLX4 methylation (p < 0.0001, p=0.0001, p=0.0004, respectively). Cox's proportional hazard regression analysis revealed that DLX4 methylation was an independent risk factor for poor prognosis regarding recurrence-free, cancer-specific, and overall survival (p < 0.0001, p=0.0005, p =0.0018, respectively).
Conclusions. Methylated DLX4 is a potential biomarker that predicts poor prognosis after curative resection of pathologic stage I NSCLC. Identification of patients with methylated DLX4 may assist stratification for appropriate adjuvant treatment strategies.

• 出版日期2015-5