Hiroaki Harada1, Kazuaki Miyamoto2, Yoshinori Yamashita3, Kiyomi Taniyama4, Hideki Ohdan5, Morihito Okada6. 1. Department of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan. Electronic address: haradah@kure-nh.go.jp. 2. Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan. 3. Department of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan. 4. Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan. 5. Department of Surgery, Hiroshima University, Hiroshima, Japan. 6. Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
Abstract
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.
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.
Authors: Rory F Kokelaar; Huw G Jones; Jeremy Williamson; Namor Williams; A Paul Griffiths; John Beynon; Gareth J Jenkins; Dean A Harris Journal: Cancer Biol Ther Date: 2018-01-19 Impact factor: 4.742