犬科启发的挥发性有机化合物化学计量分析,可用于区分小鼠和人类中的前列腺癌。
Canine-Inspired Chemometric Analysis of Volatile Organic Compounds in Urine Headspace to Distinguish Prostate Cancer in Mice and Men.
发表日期:2023 Feb 20
作者:
Mark Woollam, Amanda P Siegel, Adam Munshi, Shengzhi Liu, Sunil Tholpady, Thomas Gardner, Bai-Yan Li, Hiroki Yokota, Mangilal Agarwal
来源:
Cancers
摘要:
犬只通过嗅觉检测尿中的挥发性有机物(VOCs),可以高精准度地诊断前列腺癌。先前的研究已经通过固相微萃取(SPME)气相色谱质谱(GC-MS)技术鉴定了前列腺癌的VOCs生物标志物,但并未评估VOCs区分侵袭性癌症的能力。此外,以往的研究利用小鼠模型鉴定生物标志物,但并未确定结果是否适用于人类。为应对这些挑战,收集了患有前列腺癌的小鼠和接受前列腺癌活检的男性的尿液,通过SPME GC-MS对VOCs进行了分析。在分析之前,对比了SPME纤维/箭头,发现纤维对分子量低的VOCs具有更高的灵敏度。小鼠尿液分析表明,VOCs可以 100% 准确地区分携带肿瘤的小鼠。在人类尿液中,对六种 VOCs 进行线性判别分析可以以 75% 的灵敏度和 69% 的特异性区分前列腺癌;另一组包含七种 VOCs 的板可以以 78% 的灵敏度和 85% 的特异性区分侵袭性癌症。这些结果表明,VOCs检测前列腺癌的精准度尚可,且优于区分侵袭性肿瘤的能力。此外,人类和小鼠中VOCs结构的重合显示了小鼠模型对于鉴定生物标志物候选者具有优点。
Canines can identify prostate cancer with high accuracy by smelling volatile organic compounds (VOCs) in urine. Previous studies have identified VOC biomarkers for prostate cancer utilizing solid phase microextraction (SPME) gas chromatography-mass spectrometry (GC-MS) but have not assessed the ability of VOCs to distinguish aggressive cancers. Additionally, previous investigations have utilized murine models to identify biomarkers but have not determined if the results are translatable to humans. To address these challenges, urine was collected from mice with prostate cancer and men undergoing prostate cancer biopsy and VOCs were analyzed by SPME GC-MS. Prior to analysis, SPME fibers/arrows were compared, and the fibers had enhanced sensitivity toward VOCs with a low molecular weight. The analysis of mouse urine demonstrated that VOCs could distinguish tumor-bearing mice with 100% accuracy. Linear discriminant analysis of six VOCs in human urine distinguished prostate cancer with sensitivity = 75% and specificity = 69%. Another panel of seven VOCs could classify aggressive cancer with sensitivity = 78% and specificity = 85%. These results show that VOCs have moderate accuracy in detecting prostate cancer and a superior ability to stratify aggressive tumors. Furthermore, the overlap in the structure of VOCs identified in humans and mice shows the merit of murine models for identifying biomarker candidates.