基于拉曼光谱技术的口腔鳞癌患者血清诊断模型研究

发布时间：2018-05-26 21:16

本文选题：口腔鳞状细胞癌 + 表面增强拉曼光谱　；参考：《重庆医科大学》2017年博士论文

【摘要】：研究背景口腔鳞状细胞癌(OSCC)在全球范围内越来越普遍。OSCC的预后很大程度上依赖于早期检测。但常规口腔检查可能会延迟诊断,因为在临床上期口腔恶性病变与早期炎性疾病不易区分。在这项研究中,收集整理了2013年至2015年间重庆医科大学附属口腔医院收治的口腔鳞状细胞癌患者病例资料并继续统计分析,研究了一种新的诊断方法,利用表面增强拉曼光谱(SERS)检测癌症患者的血清样本。方法根据口腔鳞状细胞癌的诊断标准及本研究的纳入和排除标准收集病例资料,共计496例,利用SPSS 13.0进行统计分析。收集OSCC患者、腮腺粘液表皮样癌患者和正常对照组志愿者的血清样本。金纳米粒子(NPs)混合血清样本以获取高质量的表面增强拉曼光谱。成功地捕捉到135例OSCC光谱样本、90例粘液表皮样癌(MEC)样本和145例正常对照组样本。与正常对照组相比,OSCC组和MEC组存在拉曼光谱差异,差异归属于核酸,蛋白质和脂质。基于这些光谱差异和特征,主成分分析(PCA)和线性判别分析(LDA)被用来分析和分类各个组的拉曼光谱。结果发病年龄高峰主要集中在50-59岁、60-69岁及70-79岁三个年龄段之间,男女比例大概为2:1。颈部淋巴结转移率为42.9%,颈部淋巴结转移与患者年龄、发病部位、肿瘤大小与病理分期有关,具有统计学差异,P0.05。而局部复发与肿瘤大小和病理分期有关,具有统计学差异,P0.05。通过Cox比例风险回归模型分析,结果明局部复发患者的死亡风险为无局部复发患者的约122倍。与正常组相比,OSCC组和MEC组主要增加峰值归属于核酸和蛋白质的分子结构。OSCC组和MEC组对比,不同的峰值归属于类胡萝卜素和脂质的特殊分子结构。PCA-LDA分析结果表明OSCC可以成功的与正常对照组辨别,敏感性为80.7%,特异性为84.1%。交叉验证证明PCA-LDA分析的结果是可靠的。结论重庆地区口腔鳞癌患者发病年龄集中,男女比例大概为2:1。口腔鳞癌患者颈部淋巴转移率为42.9%。通过统计分析,口腔鳞癌患者颈部淋巴结转移与患者性别、发病部位、肿瘤大小及病理分期相关,而口腔鳞癌患者的局部复发则与肿瘤大小及病理分期相关。影响口腔鳞癌患者预后的相关因素为局部复发。对于OSCC、MEC和正常血清样本来说,金纳米粒子(NPs)可以作为适当的物质去捕获高质量表面增强拉曼光谱。这项研究的结果证实,通SERS结合PCA-LDA分析,对于检测和诊断OSCC有着巨大的帮助。
[Abstract]:Background: the prognosis of oral squamous cell carcinoma (OSCC) is more and more common in the world. The prognosis of OSCC depends largely on early detection. However, routine oral examination may delay diagnosis because it is not easy to distinguish malignant lesions from early inflammatory diseases. In this study, we collected and analyzed the data of patients with oral squamous cell carcinoma admitted to the affiliated Stomatological Hospital of Chongqing Medical University from 2013 to 2015, and studied a new diagnostic method. Surface enhanced Raman spectroscopy (SERS) was used to detect serum samples from cancer patients. Methods according to the diagnostic criteria of oral squamous cell carcinoma and the inclusion and exclusion criteria of this study, the data of 496 cases were collected and analyzed by SPSS 13.0. Serum samples were collected from OSCC patients, parotid mucoepidermoid carcinoma patients and normal controls. Gold nanoparticles (NPs) mixed with serum samples to obtain high quality surface enhanced Raman spectroscopy. A total of 90 mucoepidermoid carcinoma (OSCC) samples and 145 normal controls were successfully captured. The difference of Raman spectra between OSCC group and MEC group was attributed to nucleic acid, protein and lipid. Based on these spectral differences and characteristics, principal component analysis (PCA) and linear discriminant analysis (LDA) were used to analyze and classify the Raman spectra of different groups. Results the peak age of onset was mainly between 50-59 and 70-79, and the ratio of male and female was about 2: 1. The cervical lymph node metastasis rate was 42.9%. The cervical lymph node metastasis was related to the patient's age, location of disease, tumor size and pathological stage (P 0.05). However, local recurrence was related to tumor size and pathological stage (P 0.05). According to the Cox proportional risk regression model, the risk of death in patients with local recurrence was about 122-fold higher than that in patients without local recurrence. Compared with normal group, OSCC group and MEC group mainly increased the peak value attributed to the molecular structure of nucleic acid and protein. OSCC group and MEC group were compared. Different peaks were attributed to the special molecular structure of carotenoids and lipids. The results of PCA-LDA analysis showed that OSCC could be successfully distinguished from the normal control group with a sensitivity of 80.7 and a specificity of 84.1. Cross-validation proves that the results of PCA-LDA analysis are reliable. Conclusion the age of oral squamous cell carcinoma in Chongqing area is concentrated, and the ratio of male and female is about 2: 1. The cervical lymphatic metastasis rate was 42.9% in patients with oral squamous cell carcinoma. By statistical analysis, cervical lymph node metastasis was correlated with sex, location, tumor size and pathological stage of patients with oral squamous cell carcinoma, while local recurrence of patients with oral squamous cell carcinoma was correlated with tumor size and pathological stage. Local recurrence is associated with prognosis of oral squamous cell carcinoma (OSCC). For OSCC MEC and normal serum samples, gold nanoparticles (NPs) can be used as suitable materials to capture high quality surface-enhanced Raman spectra. The results of this study confirm that SERS combined with PCA-LDA analysis can be of great help in detecting and diagnosing OSCC.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R739.8

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