Optical Nanoscale Analysis of Buccal Cells: Transforming Lung Cancer Screening

描述（由申请人提供）：该项目的总体目标是开发一种人口风险分层工具，以实现有效且具有成本效益的肺癌筛查。肺癌是一种理想的恶性肿瘤筛查，因为它的患病率，可识别的危险群体（当前/以前的吸烟者），如果早期诊断，可以通过手术治愈疾病。然而，目前还没有可靠的筛查技术，比如CT扫描，这种方法成本高昂，而且会产生大量的假阳性结果。一种有吸引力的方法是利用现场致癌作用，即导致肺某一区域病变的相同遗传/环境环境会影响整个空气消化粘膜。颊（颊）粘膜是肺癌发生的“分子镜像”，尽管目前的技术还不足以将这一现象转化为微创筛查试验。我们的初步数据表明，口腔细胞纳米级结构的改变对场癌变非常敏感，因此可能作为肺癌的强有力的生物标志物。这些纳米结构的变化可以通过一种新颖的生物光子学技术，部分波光谱（PWS）显微镜以实用和高度精确的方式检测。在本研究中，我们将改进PWS技术，开发一种基于PWS可检测的纳米级变化的预测规则，该规则针对早期可治愈的肺癌进行优化。我们将验证我们的初步数据，即在人口统计学、危险因素（如吸烟强度）和非肺癌原发癌方面没有混淆。最后，我们将在病例对照和队列研究中对口腔PWS进行前瞻性验证。该项目将为未来确定的大规模多中心验证试验提供必要的数据，这些试验可以明确证明口腔PWS分析作为肺癌筛查的第一线的有效性，允许合理使用更昂贵或侵入性的工具，如CT扫描或支气管镜检查。这种新模式可能会改变肺癌筛查的临床实践，从而减轻美国人因这种恶性肿瘤而造成的巨大损失。

DESCRIPTION (provided by applicant): The overarching goal of the project is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as CT scans fraught with cost and harm from large numbers of false positives. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aerodigestive mucosa. The buccal (cheek) mucosa is a "molecular mirror" of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. Our preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and, hence, may serve as a robust biomarker for lung cancer. These nanoarchitectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy. In this study, we will refine PWS technology, develop a prediction rule based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. We will validate our preliminary data that there is no confounding with regards to demographics, risk factors (e.g. smoking intensity) and non-lung primary cancers. Finally, we will prospectively validate buccal PWS in a case control and a cohort studies. This project will provide the requisite data for future definitive large scale multicenter validation trials that could unequivocally prove the efficacy of buccal PWS analysis as the first line of screening for lung cancer allowing rational use of more expensive or intrusive tools such as CT scans or bronchoscopy. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans. PUBLIC HEALTH RELEVANCE: No existing technique allows accurate and cost-effective lung cancer screening. This project will lead towards development of a minimally invasive optical technique that would enable lung cancer screening in asymptomatic population by a simple cheek swap that can be performed in a primary care setting.