School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
Analyst. 2019 Dec 2;144(24):7447-7456. doi: 10.1039/c9an01749f.
Diagnostic tools for the detection of early-stage oesophageal adenocarcinoma (OAC) are urgently needed. Our aim was to develop an accurate and inexpensive method using biofluids (plasma, serum, saliva or urine) for detecting oesophageal stages through to OAC (squamous; inflammatory; Barrett's; low-grade dysplasia; high-grade dysplasia; OAC) using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR spectroscopy coupled with variable selection methods, with successive projections or genetic algorithms (GA) combined with quadratic discriminant analysis (QDA) were employed to identify spectral biomarkers in biofluids for accurate diagnosis in a hospital setting of different stages through to OAC. Quality metrics (Accuracy, Sensitivity, Specificity and F-score) and biomarkers of disease were computed for each model. For plasma, GA-QDA models using 15 wavenumbers achieved 100% classification for four classes. For saliva, PCA-QDA models achieved 100% for the inflammatory stage and high-quality metrics for other classes. For serum, GA-QDA models achieved 100% performance for the OAC stage using 13 wavenumbers. For urine, PCA-QDA models achieved 100% performance for all classes. Selected wavenumbers using a Student's t-test (95% confidence interval) identified a differentiation of the stages on each biofluid: plasma (929 cm-1 to 1431 cm-1, associated with DNA/RNA and proteins); saliva (1000 cm-1 to 1150 cm-1, associated with DNA/RNA region); serum (1435 cm-1 to 1573 cm-1, associated with methyl groups of proteins and Amide II absorption); and, urine (1681 cm-1 to 1777 cm-1, associated with a high frequency vibration of an antiparallel β-sheet of Amide I and stretching vibration of lipids). Our methods have demonstrated excellent efficacy for a rapid, cost-effective method of diagnosis for specific stages to OAC. These findings suggest a potential diagnostic tool for oesophageal cancer and could be translated into clinical practice.
诊断工具，用于检测早期食管腺癌（OAC）是迫切需要的。我们的目的是开发一种准确和廉价的方法，使用生物流体（血浆、血清、唾液或尿液）通过衰减全反射傅里叶变换红外（ATR-FTIR）光谱来检测食管阶段到 OAC（鳞状；炎症； Barrett 食管；低级别上皮内瘤变；高级别上皮内瘤变；OAC）。ATR-FTIR 光谱结合变量选择方法，使用连续投影或遗传算法（GA）与二次判别分析（QDA）相结合，用于识别生物流体中的光谱生物标志物，以实现医院环境中不同阶段到 OAC 的准确诊断。为每个模型计算了质量指标（准确性、敏感性、特异性和 F 分数）和疾病生物标志物。对于血浆，使用 15 个波数的 GA-QDA 模型实现了 4 类的 100%分类。对于唾液，PCA-QDA 模型实现了炎症阶段的 100%和其他类别的高质量指标。对于血清，使用 13 个波数的 GA-QDA 模型实现了 OAC 阶段的 100%性能。对于尿液，PCA-QDA 模型实现了所有类别的 100%性能。使用学生 t 检验（95%置信区间）选择的波数，在每种生物流体上识别出了不同阶段的差异：血浆（929cm-1 到 1431cm-1，与 DNA/RNA 和蛋白质相关）；唾液（1000cm-1 到 1150cm-1，与 DNA/RNA 区域相关）；血清（1435cm-1 到 1573cm-1，与蛋白质的甲基基团和酰胺 II 吸收相关）；尿液（1681cm-1 到 1777cm-1，与酰胺 I 的反平行β-折叠的高频振动和脂质的伸缩振动相关）。我们的方法已经证明了对于特定阶段到 OAC 的快速、具有成本效益的诊断方法具有优异的疗效。这些发现表明了一种用于食管癌的潜在诊断工具，并可能转化为临床实践。
