Shu Chi, Zheng Wei, Lin Kan, Lim Chwee Ming, Huang Zhiwei
Optical Bioimaging Laboratory, Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, 117576, Singapore.
Department of Otolaryngology, Singapore General Hospital, Duke-NUS Graduate Medical School, Singapore 169608.
Talanta. 2023 Jul 1;259:124561. doi: 10.1016/j.talanta.2023.124561. Epub 2023 Apr 14.
Cancer staging is important to guide treatment and for prognostication. This work aims to demonstrate the ability of rapid fiberoptic Raman endoscopy for real-time in vivo cancer staging of nasopharyngeal cancer (NPC) patients. We interrogate 278 tissue sites on the primary NPC with different cancer stages from 61 NPC patients and 50 healthy volunteers using rapid fiberoptic Raman endoscopy examination. Distinct Raman spectral differences of NPC at different cancer stages are observed through simultaneous fingerprint and high-wavenumber (FP/HW) Raman spectral measurements, reflecting the biomolecular differences of NPC tumor across various cancer stages. Raman staging model is established based on in vivo FP/HW tissue Raman spectra together with partial-least-squares linear-discriminant-analysis (PLS-LDA) and leave-one-tissue-site-out cross-validation (LOOCV). In vivo FP/HW Raman endoscopy provides an overall diagnostic accuracy of 92.81% for identifying different stages of NPC (i.e., NPC stage I&II and NPC stage III&IV) from normal nasopharynx. Specifically, the diagnostic sensitivity of 91.18% is obtained for identifying NPC stage I& II; and the sensitivity of 93.04% is achieved for classifying NPC stage III&IV from normal tissue. The key tissue biomolecular variations responsible for different NPC stages have been identified using biomolecular Raman modeling developed based on non-negative linear regression. The essential biomolecules (chondroitin sulfate, glucose, hemoglobin, oleic acid and triolein) are uncovered from the Raman spectra of NPC tissues through biomolecular modeling with significant variations (p < 0.05) between early-stage NPC (stage I and stage II) and late-stage NPC patients (stage III and stage IV). Our pivotal work demonstrates for the first time that fiberoptic Raman endoscopy is a robust analytical tool for real-time in vivo NPC staging in clinical settings.
癌症分期对于指导治疗和预后判断很重要。这项工作旨在证明快速光纤拉曼内镜用于鼻咽癌（NPC）患者实时体内癌症分期的能力。我们使用快速光纤拉曼内镜检查对61例NPC患者和50名健康志愿者的不同癌症分期的原发性NPC的278个组织部位进行了检测。通过同时进行指纹和高波数（FP/HW）拉曼光谱测量，观察到不同癌症分期的NPC有明显的拉曼光谱差异，反映了NPC肿瘤在不同癌症分期的生物分子差异。基于体内FP/HW组织拉曼光谱以及偏最小二乘线性判别分析（PLS-LDA）和留一组织部位交叉验证（LOOCV）建立了拉曼分期模型。体内FP/HW拉曼内镜从正常鼻咽部识别NPC不同分期（即NPC I&II期和NPC III&IV期）的总体诊断准确率为92.81%。具体而言，识别NPC I&II期的诊断敏感性为91.18%；从正常组织中分类NPC III&IV期的敏感性为93.04%。使用基于非负线性回归开发的生物分子拉曼模型确定了导致不同NPC分期的关键组织生物分子变化。通过生物分子建模从NPC组织的拉曼光谱中发现了基本生物分子（硫酸软骨素、葡萄糖、血红蛋白、油酸和三油酸甘油酯），早期NPC（I期和II期）和晚期NPC患者（III期和IV期）之间存在显著差异（p<0.05）。我们的关键工作首次证明光纤拉曼内镜是临床环境中用于实时体内NPC分期的强大分析工具。
