Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, Charles University, Prague, Czech Republic.
1st Surgical Department, First Faculty of Medicine, Charles University and General University Hospital, Charles University, Prague, Czech Republic.
Neoplasma. 2020 Nov;67(6):1349-1358. doi: 10.4149/neo_2020_200506N494. Epub 2020 Aug 13.
Colorectal cancer (CRC) remains a significant threat to human health because of the lack of awareness of physical examination or the limitations of an early diagnostic level. Despite the improving standard of modern medicine, mortality from CRC is still remarkably high and the prognosis remains poor in many cases because of disease detection at advanced clinical stages. Raman spectroscopy yields precise information, not only regarding the secondary structure of proteins but also regarding the discrimination between normal and malignant tissues. We investigated whether this method can be used for the diagnosis of CRC including initial stages. To acquire more detailed structural information, we tested a novel diagnostic approach based on a suitable combination of conventional methods of molecular spectroscopy (Raman and Fourier transform infrared) with advanced, highly structure-sensitive chiroptical techniques as electronic circular dichroism (ECD) and Raman optical activity (ROA) to monitor the CRC pathogenesis relating compositional, structural and conformational changes in blood biomolecules, some of which may be caused by pathological processes occurring during cancer growth, also at the beginning of the disease. Sixty-three blood plasma samples were analyzed using the combination of ECD and ROA supplemented by Raman and Fourier transform infrared (FT-IR) spectroscopies. The obtained spectra were evaluated together by linear discriminant analysis. The accuracy of sample discrimination reached 100% and the subsequent leave-one-out cross-validation resulted in 90% sensitivity and 75% specificity. There were also found the differences between the patients according to the clinical stage. The achieved results suggest a panel of promising biomarkers and indicate that chiroptical methods combined with conventional spectroscopies might be a new minimally invasive powerful tool for producing high-quality data, obtaining an accurate diagnosis of colorectal cancer through a peripheral blood sample, which is also able to determine the extent of this pathology. Further work needs to be carried out for these techniques to be implemented in the clinical setting.
结直肠癌(CRC)仍然是对人类健康的重大威胁,因为人们对体检缺乏认识或早期诊断水平有限。尽管现代医学的标准在不断提高,但CRC 的死亡率仍然很高,而且在许多情况下预后仍然很差,这是因为疾病在晚期才被发现。拉曼光谱不仅能提供有关蛋白质二级结构的精确信息,还能区分正常组织和恶性组织。我们研究了这种方法是否可用于诊断 CRC 包括早期阶段。为了获得更详细的结构信息,我们测试了一种新的诊断方法,该方法基于常规分子光谱(拉曼和傅里叶变换红外)与先进的、高度结构敏感的手性技术(电子圆二色性(ECD)和拉曼光学活性(ROA)的合适组合,以监测与血液生物分子的组成、结构和构象变化相关的 CRC 发病机制,其中一些可能是由癌症生长过程中发生的病理过程引起的,也可能是在疾病的早期引起的。使用 ECD 和 ROA 与拉曼和傅里叶变换红外(FT-IR)光谱相结合分析了 63 个血浆样本。通过线性判别分析对获得的光谱进行了综合评估。样本判别准确率达到 100%,随后的留一法交叉验证结果为 90%的灵敏度和 75%的特异性。根据临床分期,还发现了患者之间的差异。研究结果表明存在一组有前途的生物标志物,并表明手性方法与常规光谱相结合可能是一种新的微创强大工具,可用于生成高质量数据,通过外周血样准确诊断结直肠癌,并能够确定该病理学的严重程度。需要进一步开展工作,以便将这些技术应用于临床环境。