Sailer Verena, Holmes Emily Eva, Gevensleben Heidrun, Goltz Diane, Dröge Freya, de Vos Luka, Franzen Alina, Schröck Friederike, Bootz Friedrich, Kristiansen Glen, Schröck Andreas, Dietrich Dimo
Weill Medical College of Cornell University and New York Presbyterian Hospital, Department of Pathology and Laboratory Medicine, New York, NY, USA.
Weill Medical College of Cornell University and New York Presbyterian Hospital, Englander Institute for Precision Medicine, New York, NY, USA.
Oncotarget. 2016 Nov 15;7(46):75827-75838. doi: 10.18632/oncotarget.12417.
Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.
PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010).
Quantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy).
PITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.
头颈部鳞状细胞癌（HNSCC）是一种常见的恶性疾病，在进行根治性治疗后局部或远处复发风险较高。能够预测疾病转归的生物标志物可在治疗和监测策略方面为临床医生提供指导。在此，评估了PITX2和一个相邻长链非编码RNA（PANCR）的甲基化状态预测HNSCC患者总生存期的能力。
PITX2高甲基化与更好的总生存期相关（风险比，HR = 0.51，95%置信区间：0.35 - 0.74，p<0.001），而PANCR高甲基化与死亡风险增加显著相关（HR = 1.64，95%置信区间：1.12 - 2.39，p = 0.010）。
采用针对PITX2和PANCR的定量、甲基化特异性实时PCR检测，对399例接受根治性治疗（手术联合选择性辅助放化疗或确定性放化疗）的局限性或局部晚期HNSCC患者的福尔马林固定、石蜡包埋（FFPE）组织经亚硫酸氢盐转化的DNA进行检测。
PITX2和PANCR甲基化状态被证明是HNSCC患者总生存期的独立预测指标。因此，基于组织的甲基化检测可能可用于识别可能从更积极或替代治疗中获益的高死亡风险患者。
