Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy

BackgroundThis study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts.MethodsHR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis.Results and conclusionHR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra.

[1]  F. Podo Tumour phospholipid metabolism , 1999, NMR in biomedicine.

[2]  T. Bathen,et al.  Characterization of brain metastases using high‐resolution magic angle spinning MRS , 2008, NMR in biomedicine.

[3]  C. Belka,et al.  Tumour Hypoxia: Impact on Biology, Prognosis and Treatment of Solid Malignant Tumours , 2004, Oncology Research and Treatment.

[4]  H. Degani,et al.  Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. , 2002, Cancer research.

[5]  R. Kauppinen,et al.  A metabolomics perspective of human brain tumours , 2007, The FEBS journal.

[6]  C. Fyfe magic angle spinning , 2020, Catalysis from A to Z.

[7]  M. Horn Cardiac magnetic resonance spectroscopy: a window for studying physiology. , 2006, Methods in molecular medicine.

[8]  Z. Bhujwalla,et al.  Choline phospholipid metabolism: A target in cancer cells? , 2003, Journal of cellular biochemistry.

[9]  F. Sekiguchi,et al.  Antitumor activity of erlotinib in combination with capecitabine in human tumor xenograft models , 2006, Cancer Chemotherapy and Pharmacology.

[10]  H. Tost,et al.  The biochemistry of dysfunctional emotions: proton MR spectroscopic findings in major depressive disorder. , 2006, Progress in brain research.

[11]  David L. Woodruff,et al.  Beam search for peak alignment of NMR signals , 2004 .

[12]  B. Sitter,et al.  High‐resolution magic angle spinning MRS of breast cancer tissue , 2002, NMR in biomedicine.

[13]  T. Seierstad,et al.  Early changes in apparent diffusion coefficient predict the quantitative antitumoral activity of capecitabine, oxaliplatin, and irradiation in HT29 xenografts in athymic nude mice. , 2007, Neoplasia.

[14]  I. Schuppe-Koistinen,et al.  Peak alignment of NMR signals by means of a genetic algorithm , 2003 .

[15]  P. Carroll,et al.  Quantitative analysis of prostate metabolites using 1H HR‐MAS spectroscopy , 2006, Magnetic resonance in medicine.

[16]  W. Mackinnon,et al.  Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. , 1992, Biochemistry.

[17]  A Moreno,et al.  Quantitative and Qualitative Characterization of 1H NMR Spectra of Colon Tumors, Normal Mucosa and their Perchloric Acid Extracts: Decreased Levels of Myo‐inositol in Tumours can be Detected in Intact Biopsies , 1996, NMR in biomedicine.

[18]  Lee M Ellis,et al.  Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  Robin K. Harris,et al.  Encyclopedia of nuclear magnetic resonance , 1996 .

[20]  R. Kerbel Human Tumor Xenografts as Predictive Preclinical Models for Anticancer Drug Activity in Humans: Better than Commonly Perceived—But They Can Be Improved , 2003, Cancer biology & therapy.

[21]  C. Arús,et al.  1H NMR spectroscopy of colon tumors and normal mucosal biopsies; elevated taurine levels and reduced polyethyleneglycol absorption in tumors may have diagnostic significance , 1993, NMR in biomedicine.

[22]  H. Degani,et al.  Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies , 2007, International journal of cancer.

[23]  R. Gonzalez,et al.  Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Spraul,et al.  Magic Angle Spinning Proton Nuclear Magnetic Resonance Spectroscopic Analysis of Intact Kidney Tissue Samples , 1997 .

[25]  T. Bathen,et al.  Metabolic mapping by use of high-resolution magic angle spinning 1H MR spectroscopy for assessment of apoptosis in cervical carcinomas , 2007, BMC Cancer.

[26]  G. Maelandsmo,et al.  Twelve colorectal cancer cell lines exhibit highly variable growth and metastatic capacities in an orthotopic model in nude mice. , 2004, European journal of cancer.

[27]  T. Bathen,et al.  MR-determined metabolic phenotype of breast cancer in prediction of lymphatic spread, grade, and hormone status , 2007, Breast Cancer Research and Treatment.

[28]  D. Cory,et al.  Gradient, high‐resolution, magic‐angle spinning nuclear magnetic resonance spectroscopy of human adipocyte tissue , 1997, Magnetic resonance in medicine.

[29]  M. Baumann,et al.  Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[30]  L. Kèlland,et al.  Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development. , 2004, European journal of cancer.

[31]  Z. Bhujwalla,et al.  Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. , 1999, Cancer research.