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利用源自血浆或血清分析的光谱生物标志物对卵巢癌分期进行区分:衰减全反射傅里叶变换红外光谱法与变量选择方法相结合

Segregation of ovarian cancer stage exploiting spectral biomarkers derived from blood plasma or serum analysis: ATR-FTIR spectroscopy coupled with variable selection methods.

作者信息

Lima Kássio M G, Gajjar Ketan B, Martin-Hirsch Pierre L, Martin Francis L

机构信息

Centre for Biophotonics, LEC, Lancaster University, Lancaster, LA14YQ, UK.

Inst. of Chemistry, Biological Chemistry and Chemometrics, Federal University of Rio Grande do Norte, Natal, 59072-970, RN-Brazil.

出版信息

Biotechnol Prog. 2015 May-Jun;31(3):832-9. doi: 10.1002/btpr.2084. Epub 2015 Apr 29.

Abstract

Ovarian cancer is a solid tumor and a leading cause of mortality. Diagnostic tools for the detection of early stage (stage I) ovarian cancer are urgently needed. For this purpose, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) coupled with variable selection methods, successive projection algorithm or genetic algorithm (GA) combined with linear discriminant analysis (LDA), were employed to identify spectral biomarkers in blood plasma or serum samples for accurate diagnosis of different stages of ovarian cancer, histological type and segregation based on age. Three spectral datasets (stage I vs. stage II-IV; serous vs. non-serous carcinoma; and, ≤60 years vs. >60 years) were processed: sensitivity and specificity required for real-world diagnosis of ovarian cancer was achieved. Toward segregating stage I vs. stage II-IV, sensitivity and specificity (plasma blood) of 100% was achieved using a GA-LDA model with 33 wavenumbers. For serous vs. non-serous category (plasma blood), the sensitivity and specificity levels, using 29 wavenumbers by GA-LDA, were remarkable (up to 94%). For ≤60 years and >60 years categories (plasma blood), the sensitivity and specificity, using 42 wavenumbers by GA-LDA, gave complete accuracy (100%). For serum samples, sensitivity and specificity results gave relatively high accuracy (up to 91.6% stage I vs. stage II-IV; up to 93.0% serous vs. non-serous; and, up to 96.0% ≤60 years vs. >60 years) using several wavenumbers. These findings justify a prospective population-based assessment of biomarkers signatures using ATR-FTIR spectroscopy as a screening tool for stage of ovarian cancer.

摘要

卵巢癌是一种实体瘤,也是导致死亡的主要原因。目前迫切需要用于检测早期(I期)卵巢癌的诊断工具。为此,采用衰减全反射傅里叶变换红外光谱(ATR-FTIR)结合变量选择方法、连续投影算法或遗传算法(GA)与线性判别分析(LDA)相结合的方式,来识别血浆或血清样本中的光谱生物标志物,以准确诊断卵巢癌的不同阶段、组织学类型以及基于年龄的分类。对三个光谱数据集(I期与II-IV期;浆液性癌与非浆液性癌;以及≤60岁与>60岁)进行了处理:实现了卵巢癌实际诊断所需的敏感性和特异性。在区分I期与II-IV期时,使用具有33个波数的GA-LDA模型,血浆样本的敏感性和特异性达到了100%。对于浆液性与非浆液性类别(血浆样本),GA-LDA使用29个波数时,敏感性和特异性水平显著(高达94%)。对于≤60岁和>60岁类别(血浆样本),GA-LDA使用42个波数时,敏感性和特异性达到了完全准确(100%)。对于血清样本,使用多个波数时,敏感性和特异性结果给出了相对较高的准确性(I期与II-IV期高达91.6%;浆液性与非浆液性高达93.0%;≤60岁与>60岁高达96.0%)。这些发现证明了使用ATR-FTIR光谱作为卵巢癌分期筛查工具对生物标志物特征进行基于人群的前瞻性评估的合理性。

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