基于HOF-ATR-FTIR光谱学的乳腺癌的蛋白质二级结构变化及识别研究  

Study on protein secondary structure changes and discrimination of breast cancer by HOF-ATR-FTIR spectroscopy

作　　者：唐金兰 陆燕飞 包一麟 赵远 尚林伟 尹建华[1] TANG Jinlan;LU Yanfei;BAO Yilin;ZHAO Yuan;SHANG Linwei;YIN Jianhua(Department of biomedical engineering,Nanjing University of Aeronautics and Astronautics,Nanjing 210016,China;The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China)

机构地区：[1]南京航空航天大学生物医学工程系,南京211106 [2]中国科学院大学附属肿瘤医院(浙江省肿瘤医院),中国科学院肿瘤与基础医学研究所,杭州310022

出　　处：《光散射学报》2021年第2期179-186,共8页The Journal of Light Scattering

基　　金：国家自然科学基金(No.61378087);江苏省自然科学基金(No.BK20151478)资助。

摘　　要：衰减全反射傅里叶变换红外(ATR-FTIR)光谱技术可以用来直接测量生物组织的红外光谱。本研究首次采用自制的空心光纤(HOF)-ATR探针耦合FTIR光谱仪实现了健康和癌变乳腺组织原位光谱探测。利用去卷积、二阶导数和曲线拟合方法对所测光谱的酰胺I带(1700-1600 cm-1)进行了分析,获得了乳腺组织中蛋白质各二级结构的含量信息。发现癌变和正常乳腺组织的二级结构组成有明显差异,即癌变乳腺组织中β-折叠、无规卷曲和非典型螺旋的含量要低于正常乳腺组织,α-螺旋和β-转角的含量要高于正常乳腺组织。二级结构含量分析发现,乳腺癌变时胶原蛋白和丝心蛋白在减少,α-角蛋白的合成明显增加,初步揭示了相关癌变机制。进一步分别采用酰胺I带和全光谱建立偏最小二乘判别模型,发现仅用酰胺I带建立的判别模型判别准确性(81.8%)和模型稳定性都明显低于全光谱模型(97.0%)。这表明酰胺I带虽然包含蛋白质二级结构变化的大量信息,但仍不足以代替其它主要生物成分的变化以精确分辨癌变组织。本研究表明,基于HOF-ATR-FTIR光谱技术对乳腺组织中蛋白质二级结构的研究可以在分子水平上深入分析和理解乳腺组织癌变机理,并同时提供一种对组织癌变进行原位检测和精确识别的有效方法。Attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopic technique can be used to directly measure infrared spectra of biological tissues.In this study,a home-made hollow core optical fiber(HOF)-ATR probe coupled FTIR spectrometer was firstly used to achieve in-situ spectral detection of healthy and cancerous breast tissues.The deconvolution,second derivative and curve fitting methods were used to analyze the amide I band(1700-1600 cm-1)of the measured spectra for content information of each secondary structure of protein in breast tissue.The significant difference in the secondary structures was found as below.The content ofβ-sheet,random coil and atypical helix in cancerous breast tissue is lower than that in normal breast tissue,and the content ofα-helix andβ-turn is higher than that in normal breast tissue.Comparing with normal breast tissue,secondary structure-content analysis shows that collagen and fibroin decrease and alpha-keratin synthesis increases in cancerous breast tissue,preliminarily indicating the related cancerization mechanism.Furthermore,partial least squares discrimination analysis model was established by using the amide I band and the full spectra,respectively,and it was found that the distinguish accuracy(81.8%)and stability of the discriminant model established only with the amide I band were significantly lower than those of the full spectra model(97%).This indicates that although the amide I band contains a lot of information of the changes in protein secondary structure,it is still not enough to replace the changes in other major biological components to accurately distinguish cancerous tissues.The study on HOF-ATR-FTIR spectroscopic technology applied on secondary structure analysis of protein is very helpful for deeply understanding the cancerization mechanism of breast tissue at the molecular level,and provides an effective method for in-situ detection and accurate identification of tissue cancerization.

关 键 词：乳腺癌 蛋白质二级结构 红外光谱学 空心光纤衰减全反射(HOF-ATR) 癌变识别 

分 类 号：O657.33[理学—分析化学]