Abstract
Esophageal carcinoma (EC) is one of the most common malignant tumors. EC survival has remained disappointingly low because of the high malignancy of esophageal cancer and the lack of obvious clinical symptoms at an early stage. Early diagnosis is often difficult because the small tumor nodules are frequently missed. Metabonomics based on high-resolution magic-angle spinning (HRMAS) NMR has been popular for tumor detection because it is highly sensitive, provides rich biochemical information and requires no sample pretreatment. 1H HRMAS spectra of non-involved adjacent esophageal tissues and of well differentiated and moderately differentiated esophageal carcinoma tumors were recorded and analyzed by use of multivariate and statistical analysis techniques. Moderately differentiated EC tumors were found to have increased total choline, alanine, and glutamate and reduced creatine, myo-inositol, and taurine compared with non-involved adjacent tissues. Moreover, clear differences between the metabonomic profiles of EC tissues enabled tumor differentiation. Furthermore, the integral Gly/MI ratio for samples of different tissue types were statistically significantly different; this was sufficient both for distinguishing non-involved tissues from esophageal carcinoma and for classification of well differentiated and moderately differentiated EC tumors.
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Quint LE, Hepburn LM, Francis IR, Whyte RI, Orringer MB (1995) Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma. Cancer 76(7):1120–1125
Wang L, Zhou Q, Yang C (1997) Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area. J Cell Biochem Suppl 28(1):159–165
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60(5):277–300
Yamada I, Izumi Y, Kawano T, Yoshino N, Tetsumura A, Ohashi K, Shibuya H (2001) Superficial esophageal carcinoma: an in vitro study of high-resolution MR imaging at 1.5 T. J Magn Reson Imaging 13(2):225–231
Meyenberger C, Fantin AC (2000) Esophageal carcinoma: current staging strategies. Recent Results Cancer Res 155(1):63–72
Margulies C, Kim R, Reynolds JC (1996) Early detection and management of esophageal cancer. Compr Ther 22(9):565–578
Chen LQ, Hu CY, Ghadirian P, Duranceau A (1999) Early detection of esophageal squamous cell carcinoma and its effects on therapy: an overview. Dis Esophagus 12(3):161–167
May A, Ell C (2006) Diagnosis and treatment of early esophageal cancer. Curr Opin Gastroenterol 22(4):433–436
McCann P, Stafinski T, Wong C, Menon D (2011) The safety and effectiveness of endoscopic and non-endoscopic approaches to the management of early esophageal cancer: a systematic review. Cancer Treat Rev 37(1):11–62
Kim MJ, Lee SJ, Lee JH, Kim SH, Chun HK, Kim SH, Lim HK, Yun SH (2012) Detection of rectal cancer and response to concurrent chemoradiotherapy by proton magnetic resonance spectroscopy. Magn Reson Imaging 30(6):848–853
Pope WB, Prins RM, Albert Thomas M, Nagarajan R, Yen KE, Bittinger MA, Salamon N, Chou AP, Yong WH, Soto H, Wilson N, Driggers E, Jang HG, Su SM, Schenkein DP, Lai A, Cloughesy TF, Kornblum HI, Wu H, Fantin VR, Liau LM (2012) Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neurooncol 107(1):197–205
Arteaga de Castro CS, van den Bergen B, Luijten PR, van der Heide UA, van Vulpen M, Klomp DW (2012) Improving SNR and B1 transmit field for an endorectal coil in 7 T MRI and MRS of prostate cancer. Magn Reson Med 68(1):311–318
Canese R, Pisanu ME, Mezzanzanica D, Ricci A, Paris L, Bagnoli M, Valeri B, Spada M, Venditti M, Cesolini A, Rodomonte A, Giannini M, Canevari S, Podo F, Iorio E (2012) Characterisation of in vivo ovarian cancer models by quantitative 1H magnetic resonance spectroscopy and diffusion-weighted imaging. NMR Biomed 25(4):632–642
Gao H, Dong B, Jia J, Zhu H, Diao C, Yan Z, Huang Y, Li X (2012) Application of ex vivo (1)H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases. J Cancer Res Clin Oncol 138(5):753–761
Mukherji SK, Schiro S, Castillo M, Kwock L, Muller KE, Blackstock W (1999) Proton MR spectroscopy of squamous cell carcinoma of the extracranial head and neck: in vitro and in vivo studies. J Neuroophthalmol 19(2):113–119
Doran ST, Falk GL, Somorjai RL, Lean CL, Himmelreich U, Philips J, Russell P, Dolenko B, Nikulin AE, Mountford CE (2003) Pathology of Barrett's esophagus by proton magnetic resonance spectroscopy and a statistical classification strategy. Am J Surg 185(3):232–238
Zhang J, Bowers J, Liu L, Wei S, Gowda GA, Hammoud Z, Raftery D (2012) Esophageal cancer metabolite biomarkers detected by LC–MS and NMR methods. PLoS One 7(1):e30181
Yang Y, Li C, Nie X, Feng X, Chen W, Yue Y, Tang H, Deng F (2007) Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis. J Proteome Res 6:2605–2614
Grinde MT, Moestue SA, Borgan E, Risa Ø, Engebraaten O, Gribbestad IS (2011) 13C high-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns. NMR Biomed 24(10):1243–1252
Sitter B, Bathen TF, Singstad TE, Fjøsne HE, Lundgren S, Halgunset J, Gribbestad IS (2010) Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy. NMR Biomed 23(4):424–431
Chen W, Lou H, Zhang H, Nie X, Lan W, Yang Y, Xiang Y, Qi J, Lei H, Tang H, Chen F, Deng F (2011) Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition. Sci China Life Sci 54(7):606–616
Levin YS, Albers MJ, Butler TN, Spielman D, Peehl DM, Kurhanewicz J (2009) Methods for metabolic evaluation of prostate cancer cells using proton and (13)C HR-MAS spectroscopy and [3-(13)C] pyruvate as a metabolic substrate. Magn Reson Med 62(5):1091–1098
Wang Y, Tang H, Holmes E, Lindon JC, Turini ME, Sprenger N, Bergonzelli G, Fay LB, Kochhar S, Nicholson JK (2005) Biochemical characterization of rat intestine development using high-resolution magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis. J Proteome Res 4(4):1324–1329
Yakoub D, Keun HC, Goldin R, Hanna GB (2010) Metabolic profiling detects field effects in non-dysplastic tissue from esophageal cancer patients. Cancer Res 70(22):9129–9136
Tosi MR, Bottura G, Lucchi P, Battaglia A, Giorgianni P (2001) Biochemical characterization of human renal tumors by in vitro nuclear magnetic resonance. J Mol Struct 565:323–327
Sitter B, Bathen T, Hagen B, Arentz C, Skjeldestad FE, Gribbestad IS (2004) Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy. Magma 16(4):174–181
Asten JJ, Cuijpers V, Hulsbergen-van de Kaa C, Soede-Huijbregts C, Witjes JA, Verhofstad A, Heerschap A (2008) High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies. MAGMA 21(6):435–442
Opstad KS, Bell BA, Griffiths JR, Howe FA (2008) An assessment of the effects of sample ischaemia and spinning time on the metabolic profile of brain tumour biopsy specimens as determined by high-resolution magic angle spinning (1)H NMR. NMR Biomed 21(10):1138–1147
Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Humpfer E, Spraul M, Carreira IM, Melo JB, Bernardo J, Gomes A, Sousa V, Carvalho L, Duarte IF (2010) Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J Proteome Res 9(1):319–332
Yokota H, Guo J, Matoba M, Higashi K, Tonami H, Nagao Y (2007) Lactate, choline, and creatine levels measured by vitro 1H-MRS as prognostic parameters in patients with non-small-cell lung cancer. Magn Reson Imaging 25(5):992–999
Chen W, Zu Y, Huang Q, Chen F, Wang G, Lan W, Bai C, Lu S, Yue Y, Deng F (2011) Study on metabonomic characteristics of human lung cancer using high resolution magic-angle spinning 1H NMR spectroscopy and multivariate data analysis. Magn Reson Med 66(6):1531–1540
Podo F (1999) Tumour phospholipid metabolism. NMR Biomed 12(7):413–439
Lehnhardt FG, Rohn G, Ernestus RI, Grune M, Hoehn M (2001) 1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components. NMR Biomed 14(5):307–317
Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS (2006) Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed 19(1):30–40
Semenova NA, Dydykina IY, Dederer LY, Tikhomirov AG, Gorbunova VA, Laktionova KP, Gorbacheva LB (2000) The use of 1H-NMR spectroscopy for predicting the efficiency of neoadjuvant chemotherapy of breast cancer. Bull Exp Biol Med 130(7):701–704
Acknowledgements
We acknowledge financial support from the National Natural Science Foundation of China (21005022, 81073024, 30900764), the Guangdong Natural Science Foundation (S2011010002512), and the Foundation of State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (T151003). We are also grateful for excellent suggestions and comments made by two anonymous referees which enabled us to further improve the manuscript.
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Yang, Y., Wang, L., Wang, S. et al. Study of metabonomic profiles of human esophageal carcinoma by use of high-resolution magic-angle spinning 1H NMR spectroscopy and multivariate data analysis. Anal Bioanal Chem 405, 3381–3389 (2013). https://doi.org/10.1007/s00216-013-6774-8
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DOI: https://doi.org/10.1007/s00216-013-6774-8