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利用表面增强拉曼光谱和支持向量机进行无标记血清检测以用于腮腺肿瘤的术前诊断

Label-free blood serum detection by using surface-enhanced Raman spectroscopy and support vector machine for the preoperative diagnosis of parotid gland tumors.

作者信息

Yan Bing, Li Bo, Wen Zhining, Luo Xianyang, Xue Lili, Li Longjiang

机构信息

Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hosipital of Xiamen University, Xiamen, China.

State Key Laboratory of Oral disease, Sichuan University, Chengdu, Sichuan, China.

出版信息

BMC Cancer. 2015 Oct 5;15:650. doi: 10.1186/s12885-015-1653-7.

DOI:10.1186/s12885-015-1653-7
PMID:26438216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4595250/
Abstract

BACKGROUND

It is difficult for the parotid gland neoplasms to make an accurate preoperative diagnosis due to the restriction of biopsy in the parotid gland neoplasms. The aim of this study is to apply the surface-enhanced Raman spectroscopy (SERS) method for the blood serum biochemical detection and use the support vector machine for the analysis in order to develop a simple but accurate blood serum detection for preoperative diagnosis of the parotid gland neoplasms.

METHODS

The blood serums were collected from four groups: the patients with pleomorphic adenoma, the patients with Warthin's tumor, the patients with mucoepidermoid carcinoma and the volunteers without parotid gland neoplasms. Au nanoparticles (Au NPs) were mixed with the blood serum as the SERS active nanosensor to enhance the Raman scattering signals produced by the various biochemical materials and high quality SERS spectrum were obtained by using the Raman microscope system. Then the support vector machine was utilized to analyze the differences of the SERS spectrum from the blood serum of different groups and established a diagnostic model to discriminate the different groups.

RESULTS

It was demonstrated that there were different intensities of SERS peaks assigned to various biochemical changes in the blood serum between the parotid gland tumor groups and normal control group. Compared with the SERS spectra of the normal serums, the intensities of peaks assigned to nucleic acids and proteins increased in the SERS spectra of the parotid gland tumor serums, which manifested the differences of the biochemical metabolites in the serum from the patients with parotid gland tumors. When the leave-one-sample-out method was used, support vector machine (SVM) played an outstanding performance in the classification of the SERS spectra with the high accuracy (84.1 % ~ 88.3 %), sensitivity (82.2 % ~ 97.4 %) and specificity (73.7 % ~ 86.7 %). Though the accuracy, sensitivity and specificity decreased in the leave-one-patient-out cross validation, the mucoepidermoid carcinoma was still easier to diagnose than other tumors.

DISCUSSION

The specific molecular differences of parotid gland tumors and normal serums were significantly demonstrated through the comparison between the various SERS spectra.But compared with the serum SERS spectra reported in the other studies, some differences exist between the spectra in this study and the ones reported in the lietratures. These differences may result from the various nano-particles, the different preparation of serum and equipment parameters, and we could need a further research to find an exact explanation.Based on the SERS spectra of the serum samples, SVM have shown a giant potential to diagnose the parotid gland tumors in our preliminary study. However, different cross validaiton methods could effect the accuracy and a further study involing a great number of samples should be needed.

CONCLUSIONS

This exploratory research demonstrated the great potential of SERS combined with SVM into a non-invasive clinical diagnostic method for preoperative diagnosis of parotid gland tumors. And the internal relation between the spectra and patients should be established in the further study.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/21e2d06e7787/12885_2015_1653_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/0dadd50c179b/12885_2015_1653_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/2c5aa3eb04bd/12885_2015_1653_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/21e2d06e7787/12885_2015_1653_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/0dadd50c179b/12885_2015_1653_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/2c5aa3eb04bd/12885_2015_1653_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2225/4595250/21e2d06e7787/12885_2015_1653_Fig3_HTML.jpg
摘要

背景

由于腮腺肿瘤活检的限制,术前准确诊断腮腺肿瘤较为困难。本研究旨在应用表面增强拉曼光谱(SERS)方法进行血清生化检测,并使用支持向量机进行分析,以开发一种简单而准确的血清检测方法用于腮腺肿瘤的术前诊断。

方法

收集四组血清:多形性腺瘤患者、沃辛瘤患者、黏液表皮样癌患者以及无腮腺肿瘤的志愿者。将金纳米颗粒(Au NPs)与血清混合作为SERS活性纳米传感器,以增强各种生化物质产生的拉曼散射信号,并使用拉曼显微镜系统获得高质量的SERS光谱。然后利用支持向量机分析不同组血清SERS光谱的差异,并建立诊断模型以区分不同组。

结果

结果表明,腮腺肿瘤组与正常对照组血清中,归因于各种生化变化的SERS峰强度不同。与正常血清的SERS光谱相比,腮腺肿瘤血清的SERS光谱中归因于核酸和蛋白质的峰强度增加,这表明腮腺肿瘤患者血清中生化代谢物存在差异。当采用留一法时,支持向量机(SVM)在SERS光谱分类中表现出色,具有较高的准确率(84.1%88.3%)、灵敏度(82.2%97.4%)和特异性(73.7%~86.7%)。尽管在留一患者交叉验证中准确率、灵敏度和特异性有所下降,但黏液表皮样癌仍比其他肿瘤更容易诊断。

讨论

通过比较各种SERS光谱,显著证明了腮腺肿瘤与正常血清之间的特定分子差异。但与其他研究报道的血清SERS光谱相比,本研究中的光谱与文献报道的光谱存在一些差异。这些差异可能源于各种纳米颗粒、血清制备方法和设备参数的不同,我们可能需要进一步研究以找到确切解释。基于血清样本的SERS光谱,在我们的初步研究中,支持向量机在诊断腮腺肿瘤方面显示出巨大潜力。然而,不同的交叉验证方法可能会影响准确率,需要进一步开展涉及大量样本的研究。

结论

这项探索性研究证明了SERS结合SVM作为一种非侵入性临床诊断方法用于腮腺肿瘤术前诊断的巨大潜力。在进一步研究中应建立光谱与患者之间的内在联系。

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