基于磁共振波谱和主成分分析的胰腺癌细胞对放射治疗反应的代谢组学研究
Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis.
机构信息
Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
出版信息
World J Gastroenterol. 2013 Jul 14;19(26):4200-8. doi: 10.3748/wjg.v19.i26.4200.
AIM
To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS (1)H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect.
METHODS
The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm(3), the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. (1)H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared.
RESULTS
Compared with (1)H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the (1)H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased.
CONCLUSION
The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.
目的
利用高分辨魔角旋转质子磁共振波谱（HRMAS (1)H NMR）结合主成分分析（PCA）技术研究裸鼠人胰腺癌细胞移植瘤放疗前后的代谢轮廓，评估放疗效果。
方法
将人胰腺癌细胞 SW1990 接种于裸鼠皮下，建立裸鼠人胰腺癌细胞移植瘤模型。当肿瘤体积达到 800mm(3)时，给予不同剂量的放疗。2 周后，制备肿瘤组织切片进行 NMR 测量。采用 (1)H NMR 和 PCA 技术检测放疗后肿瘤组织代谢轮廓的变化，比较正常胰腺、胰腺肿瘤组织和放疗后胰腺肿瘤组织的代谢轮廓。
结果
与正常裸鼠胰腺的 (1)H NMR 图谱相比，胰腺癌组的胆碱、牛磺酸、丙氨酸、异亮氨酸、亮氨酸、缬氨酸、乳酸和谷氨酸水平升高，而磷酸胆碱、甘油磷酸胆碱和甜菜碱则呈相反趋势。磷酸胆碱与肌酸的比值和甘油磷酸胆碱与肌酸的比值在胰腺癌组中明显降低。进一步评估三种不同辐射剂量治疗后的组织代谢谱，(1)H NMR 图谱中未见代谢物明显变化，而肿瘤生长抑制与辐射剂量呈正相关。然而，PCA 结果表明，随着辐射剂量的增加，胆碱和甜菜碱的水平降低，而乙酸的水平显著增加。
结论
该联合方法具有早期诊断和评估胰腺癌对放疗反应的潜力。
Zotero 插件