Promoter methylation of genes in bronchial lavages: A marker for early diagnosis of primary and relapsing non-small cell lung cancer?
Promoter methylation of genes in bronchial lavages: A marker for early diagnosis of primary and relapsing non-small cell lung cancer?
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DOI：
10.1016/j.lungcan.2005.05.019
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发表时间：
2005-11-01
期刊：
影响因子：
5.3
通讯作者：
Favrot, MC
中科院分区：
文献类型：
--
作者：
de Fraipont, F;Moro-Sibilot, D;Favrot, MC
一项包括计算机断层扫描（CT）、自体荧光支气管镜检查、活检和支气管灌洗液（BL）采集的前瞻性筛查项目启动了，其特定目标是确定用于早期检测非小细胞肺癌的生物标志物。我们报告并讨论了对首批126名患者进行的p16、死亡相关蛋白激酶（DAPK）、O⁶ - 甲基鸟嘌呤 - DNA甲基转移酶（MGMT）、脆性组氨酸三联体（FHIT）和腺瘤性结肠息肉病（APC）甲基化分析的结果：其中77人处于癌症高风险状态，49人在原发性癌症切除术后接受随访。在49%的支气管灌洗液、53%的当前吸烟者和43%的既往吸烟者中发现了阳性结果。在存在周围型肿瘤的情况下，只有38%的支气管灌洗液异常，而在存在中央型肿瘤时这一比例为73%，在存在癌前病变时为50%，在无病变时为47%。FHIT甲基化是一个早期事件，在有或无病变的患者的三分之一支气管灌洗液以及肿瘤中均有观察到。APC甲基化是一个晚期事件，在33%的肿瘤中观察到，但在支气管灌洗液中很少见。p16在17%的支气管灌洗液中甲基化，但在48%的肿瘤中甲基化；DAPK在15%的支气管灌洗液和22%的肿瘤中甲基化。MGMT甲基化很少见。在癌症手术后接受随访的患者中，14人病情缓解且支气管灌洗液恢复正常，而3人的支气管灌洗液呈阳性且中央型肿瘤复发。因此，支气管灌洗液中的基因甲基化可能有助于检测中央型肿瘤，但CT对于周围型癌症的检测至关重要。（c）2005爱思唯尔爱尔兰有限公司。保留所有权利。
A prospective screening program, including CT, autofluorescent bronchoscopy, biopsies and bronchial lavage (BL) collection, was initiated with the specific goal of identifying biomarkers for the early detection of non-small cell lung cancer. We report and discuss the results of p16, DAPK, MGMT, FHIT and APC methytation analysis in the 126 first patients: 77 at high risk of cancer and 49 followed up after primary cancer resection.Positive results were found in 49% of BLs, 53% in current smokers and 43% in former smokers. In presence of peripheral tumours, only 38% of BLs were abnormal versus 73% in presence of central tumours, 50% in presence of preneoplasic lesions and 47% in absence of lesions. FHIT methytation was an early event, observed in one-third of the BLs from patients with or without lesions as well as in tumours. APC methylation was a late event observed in 33% of tumours but rarely in BLs. p16 was methylated in 17% of BLs but in 48% of tumours; DAPK in 15% of BL and 22% of tumours. MGMT methylation was rare. Among patients followed up after, cancer surgery, 14 were in remission with normalised BL, whereas three had positive BLs. and relapsed with a central tumour.Thus, gene methylation in BL might help to detect central tumors but a CT is crucial for peripheral cancer detection. (c) 2005 Elsevier Ireland Ltd. All rights reserved.