Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
Carcinogenesis. 2010 May;31(5):864-70. doi: 10.1093/carcin/bgq051. Epub 2010 Mar 2.
Head and neck cancer represents 3.3% of all new malignancies and 2.0% of cancer deaths in the USA, the majority of which are squamous in origin. The overall 5 year survival is 60% and worsens with increasing stage at diagnosis. Thus, novel biomarkers for early detection of squamous cell carcinoma of the head and neck (SCCHN) are needed. MicroRNA-137 (miR-137) plays a role in cell cycle control and seems to undergo promoter methylation in oral squamous cell carcinoma tissue. The main objectives of this study were to ascertain whether miR-137 promoter methylation is detectable in oral rinse samples, assess its association with SCCHN and identify potential risk factors for its occurrence. Oral rinse samples were collected from 99 SCCHN patients with no prior history of cancer and 99 cancer-free controls, frequency matched on gender; tumor tissue for 64 patients was also tested. Methylation of the miR-137 promoter, assessed using methylation-specific polymerase chain reaction, was detected in 21.2% oral rinses from SCCHN patients and 3.0% from controls [odds ratio (OR) = 4.80, 95% confidence interval (CI): 1.23-18.82]. Among cases, promoter methylation of miR-137 was associated with female gender (OR = 5.30, 95% CI: 1.20-23.44) and inversely associated with body mass index (BMI) (OR = 0.88, 95% CI: 0.77-0.99). Promoter methylation of miR-137 appears to be a relatively frequently detected event in oral rinse of SCCHN patients and may have future utility as a biomarker in DNA methylation panels. The observed associations with gender and BMI help to shed light on potential risk factors for an altered methylation state in SCCHN.
头颈部癌症占美国所有新发恶性肿瘤的 3.3%和癌症死亡的 2.0%,其中大多数起源于鳞状细胞。总体 5 年生存率为 60%,随着诊断时分期的增加而恶化。因此,需要新的生物标志物来早期检测头颈部鳞状细胞癌(SCCHN)。microRNA-137(miR-137)在细胞周期控制中发挥作用,似乎在口腔鳞状细胞癌组织中经历启动子甲基化。本研究的主要目的是确定 miR-137 启动子甲基化是否可在口腔冲洗样本中检测到,评估其与 SCCHN 的关联,并确定其发生的潜在危险因素。采集了 99 例无癌症病史的 SCCHN 患者和 99 例无癌症对照者的口腔冲洗样本,按性别进行频数匹配;还对 64 例患者的肿瘤组织进行了检测。使用甲基化特异性聚合酶链反应评估 miR-137 启动子的甲基化,在 21.2%的 SCCHN 患者的口腔冲洗液中检测到甲基化,而在对照组中为 3.0%[比值比(OR)=4.80,95%置信区间(CI):1.23-18.82]。在病例中,miR-137 启动子甲基化与女性性别(OR=5.30,95%CI:1.20-23.44)相关,与体重指数(BMI)呈负相关(OR=0.88,95%CI:0.77-0.99)。miR-137 启动子甲基化似乎是 SCCHN 患者口腔冲洗液中相对频繁检测到的事件,并且可能作为 DNA 甲基化组中的生物标志物具有未来的应用价值。观察到的与性别和 BMI 的关联有助于阐明 SCCHN 中甲基化状态改变的潜在危险因素。