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通过 ATR-FTIR 光谱法检测卵巢癌(±新辅助化疗效果):大患者队列中血液和尿液生物流体的比较分析。

Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort.

机构信息

Department of Obstetrics and Gynaecology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, PR2 9HT, UK.

School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.

出版信息

Anal Bioanal Chem. 2021 Aug;413(20):5095-5107. doi: 10.1007/s00216-021-03472-8. Epub 2021 Jul 1.

Abstract

Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy-NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids' ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time. ATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy.

摘要

卵巢癌仍然是最致命的妇科恶性肿瘤,因为其在早期阶段的及时检测仍然难以实现。生物流体的衰减全反射傅里叶变换红外(ATR-FTIR)光谱学以前已应用于卵巢癌诊断的初步研究中,取得了有希望的结果。在此,通过在大型患者队列中应用 ATR-FTIR 光谱学进一步研究了这些初步发现。通过对 116 名卵巢癌患者和 307 名良性妇科疾病患者的血浆和血清以及尿液进行测量,获得了光谱。初步化学计量分析显示,未经化疗(n=71)和接受新辅助化疗-NACT(n=45)的卵巢癌患者的光谱存在明显差异,因此分别将这些组与良性对照进行比较。具有盲预测模型验证的分类算法表明,血清是最好的生物流体,对卵巢癌检测的灵敏度为 76%,特异性为 98%,而尿液的性能较差。NACT 卵巢癌组的血浆和血清灵敏度下降表明 ATR-FTIR 光谱有潜力识别与化疗相关的光谱变化。用于识别生物标志物的回归系数图的比较表明,糖蛋白(如 CA125)是卵巢癌检测的主要分类器,并且是导致 NACT 患者和良性对照之间光谱差异较小的原因。这项研究证实了生物流体 ATR-FTIR 光谱学(主要是血清)以高精度诊断卵巢癌的能力,并首次证明了其在监测化疗反应中的潜力。血清 ATR-FTIR 光谱能够很好地区分卵巢癌与良性对照,新辅助化疗后差异减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b1/8405472/3305149cfa3d/216_2021_3472_Figa_HTML.jpg

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