Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer.
Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer.
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DOI：
10.1053/j.gastro.2009.11.010
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发表时间：
2010-03
期刊：
影响因子：
29.4
通讯作者：
Wong DT
中科院分区：
文献类型：
--
作者：
Zhang L;Farrell JJ;Zhou H;Elashoff D;Akin D;Park NH;Chia D;Wong DT
早期胰腺癌检测技术的缺乏总是导致在初步诊断时出现典型的不治之症临床表现。迫切需要用于早期检测的新策略和生物标志物。在这项研究中，我们进行了前瞻性样本收集和回顾性盲法验证，以评估唾液转录组生物标志物用于可切除胰腺癌非侵入性检测的性能和翻译效用。使用Affytek HG U133 Plus 2.0阵列分析转录组并发现唾液上清液中改变的基因表达。从微阵列研究中发现的生物标志物进行了临床验证，使用30个胰腺癌，30个慢性胰腺炎和30个健康对照的独立样本集。发现并验证了12种mRNA生物标志物。具有四种mRNA生物标志物（KRAS、MBD3L2、ACRV 1和DPM 1）的组合的逻辑回归模型可以区分胰腺癌患者与非癌症受试者（慢性胰腺炎和健康对照），产生0.971的ROC曲线AUC值，具有90.0%的灵敏度和95.0%的特异性。唾液标志物对可切除胰腺癌的检测具有鉴别能力，具有较高的特异性和敏感性。该报告提供了唾液生物标志物用于系统性癌症非侵入性检测的概念证明，并为预测模型验证研究以及随后的关键临床验证铺平了道路。
Lack of detection technology for early pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. New strategies and biomarkers for early detection are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation to evaluate the performance and translational utilities of salivary transcriptomic biomarkers for the non-invasive detection of resectable pancreatic cancer. The Affymetrix HG U133 Plus 2.0 Array was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Biomarkers discovered from the microarray study were subjected to clinical validation using an independent sample set of 30 pancreatic cancer, 30 chronic pancreatitis and 30 healthy controls. Twelve mRNA biomarkers were discovered and validated. The logistic regression model with the combination of four mRNA biomarkers (KRAS, MBD3L2, ACRV1 and DPM1) could differentiate pancreatic cancer patients from non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.971 with 90.0% sensitivity and 95.0% specificity. The salivary biomarkers possess discriminatory power for the detection of resectable pancreatic cancer, with high specificity and sensitivity. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of a systemic cancer and paves the way for prediction model validation study followed by pivotal clinical validation.
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