Brief Article
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World J Gastroenterol. Jul 14, 2013; 19(26): 4200-4208
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4200
Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis
Xin-Hong He, Wen-Tao Li, Ya-Jia Gu, Bao-Feng Yang, Hui-Wen Deng, Yi-Hua Yu, Wei-Jun Peng
Xin-Hong He, Wen-Tao Li, Ya-Jia Gu, Bao-Feng Yang, Wei-Jun Peng, Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Hui-Wen Deng, Yi-Hua Yu, Shanghai Key Laboratory of Functional Magnetic Resonance Imaging, Physics Department, East China Normal University, Shanghai 200062, China
Author contributions: He XH performed the majority of the experiments; Li WT, Gu YJ, Yang BF, Deng HW and Yu YH provided vital reagents and analytical tools, and were also involved in editing the manuscript; Peng WJ designed the study and wrote the manuscript.
Supported by The Medical Imageology Special Purpose Foundation of Cancer Hospital/Cancer Institute Fudan University, No. YX200802
Correspondence to: Wei-Jun Peng, MD, Department of Radiology, Fudan University Shanghai Cancer Center, No. 270, Dong’an Road, Shanghai 200032, China.
Telephone: +86-21-64175590-3430 Fax: +86-21-64433384
Received: December 25, 2012
Revised: March 22, 2013
Accepted: April 27, 2013
Published online: July 14, 2013

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 1H 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 mm3, the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H 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 1H 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 1H 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.

Keywords: High-resolution magic angle spinning proton magnetic resonance spectroscopy, Principal components analysis, Pancreatic cancer, Radiotherapy

Core tip: In the present study, for the first time to our knowledge, high-resolution magic angle spinning proton magnetic resonance spectroscopy and principal components analysis were combined to highlight metabolite profiles of pancreatic cancer after radiotherapy, by analyzing the correlation between radiotherapy effect and metabolic change, and optimizing the therapeutic scheme. The results showed that metabolic profile changes of pancreatic cancer after radiotherapy were closely correlated with therapeutic effect. The outcome of the study is both interesting and beneficial to pathological research, early diagnosis, and therapy evaluation of pancreatic diseases.