协和医学杂志

2017, v.8(Z2) 268-273

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傅里叶变换红外光谱对卵巢癌肿瘤异质性诊断价值的实验室研究
Laboratory Study for Analysis of Intra-tumor Heterogeneity of Ovarian Cancer by Fourier Transform Infrared Spectroscopy

李蕾;白会敏;翁诗甫;杨丽敏;吴瑾光;徐怡庄;沈铿;
LI Lei;BAI Hui-min;WENG Shi-fu;YANG Li-min;WU Jin-guang;XU Yi-zhuang;SHEN Keng;Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;College of Chemistry and Molecular Engineering,Peking University;School of Physics,Peking University;

摘要(Abstract):

目的研究卵巢癌异质性细胞群傅里叶变换红外光谱(fourier transform infrared spectroscopy,FTIR)的异同,为异质性卵巢癌的临床诊断提供新的途径。方法对由人卵巢癌细胞系A2780所建立的高、低侵袭/迁移能力的细胞亚群(A-H和A-L)进行裸鼠体内成瘤实验和体外Transwell实验鉴定,利用FTIR技术进行检测,使用Omnic软件将二者的红外光谱进行对照解析。结果 A-H与A-L相比,细胞侵袭性更强(2.211±0.256比0.149±0.097,P=0.0003);迁移活性更高(2.412±0.298比0.337±0.079,P=0.0005);成瘤体积更大[(2.42±0.43)cm比(0.63±0.22)cm,P<0.0001]。红外光谱图显示,A-H细胞核酸吸收峰1086和1240 cm-1强度比A-L更高(0.359±0.014比0.323±0.018,P=0.020;0.343±0.010比0.317±0.012,P=0.021);蛋白质酰胺Ⅰ带1655 cm-1的吸收峰强度更高(1.710±0.024比1.640±0.017,P=0.045);与脂类相关的2925和2853 cm-1谱带吸收峰强度更高(0.669±0.025比0.613±0.016,P=0.034;0.397±0.008比0.376±0.010,P=0.039)。A-H细胞蛋白质二级结构β-折叠和转角结构的含量比A-L细胞更高(22.50±0.54比21.30±0.50,P=0.037;50.00±1.12比47.70±0.76,P=0.029),无规卷曲含量更低(8.50±0.82比11.50±1.32,P=0.011)。结论 FTIR可以快速揭示异质性卵巢癌细胞群的分子组成和结构方面的差异,为其表征提供可靠信息,可能为临床诊断和预后判断提供新的途径。
Objective Our study aimed to establish a potential way of fourier transform infrared( FTIR)spectra to diagnose malignant tumors. Methods Ovarian cancer cell subclones with high( A-H) or low( A-L)malignant potential were confirmed by Matrigel invasive/migratory assay in vitro and the tumor xenograft model in vivo. FTIR spectra of cells was recorded and analyzed in the region from 600 cm-1to 4000 cm-1. Results A-Hcells were confirmed to have higher invasive and migratory activities in vitro compared with A-L cells( 2. 211 ±0. 256 vs. 0. 149±0. 097,P = 0. 0003; 2. 412±0. 298 vs. 0. 337±0. 079,P = 0. 0005). A-H-derived tumors were significantly larger than A-L-derived tumors( 2. 42 cm±0. 43 cm vs. 0. 63 cm±0. 22 cm,P<0. 0001). Significant spectral differences between A-H and A-L cells were observed in the band intensity of 1086 cm-1and 1240 cm-1( 0. 359±0. 014 vs. 0. 323±0. 018,P = 0. 020; 0. 343±0. 010 vs. 0. 317±0. 012,P = 0. 021),as well as in that of 1655 cm-1( 1. 710±0. 024 vs. 1. 640±0. 017,P= 0. 045),2925 cm-1( 0. 669±0. 025 vs. 0. 613±0. 016,P = 0. 034) and 2853cm-1( 0. 397±0. 008 vs. 0. 376±0. 010,P= 0. 039),which indicated higher amounts and synthesis of nucleic acids,proteins and lipids in A-H cells. The amount of secondary protein structures of β-sheet and turns in A-H was higher than that in A-L( 22. 50±0. 54 vs. 21. 30±0. 50,P = 0. 037; 50. 00±1. 12 vs. 47. 70±0. 76,P = 0. 029). The amount of random coil component of protein in A-H was lower than that in A-L( 8. 50±0. 82 vs. 11. 50±1. 32,P = 0. 011).Conclusions FTIR quickly provides important and reliable information about heterogeneous ovarian cancerous cells on the difference in molecular components and structures. The findings of this study demonstrate the potential use of infrared spectroscopy in differentiating ovarian tumors at different developing stages.

关键词(KeyWords): 傅里叶变换红外光谱;卵巢癌;肿瘤异质性;临床诊断
fourier transform infrared;ovarian cancer;tumor heterogeneity;clinical diagnoses

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年科学基金项目(81502254);国家自然科学基金面上项目(81572576)

作者(Author): 李蕾;白会敏;翁诗甫;杨丽敏;吴瑾光;徐怡庄;沈铿;
LI Lei;BAI Hui-min;WENG Shi-fu;YANG Li-min;WU Jin-guang;XU Yi-zhuang;SHEN Keng;Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;College of Chemistry and Molecular Engineering,Peking University;School of Physics,Peking University;

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