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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

Therese Seierstad1,2 email, Kathrine Røe3 email, Beathe Sitter4 email, Jostein Halgunset5 email, Kjersti Flatmark6,7,8 email, Anne H Ree7,8 email, Dag Rune Olsen8,9 email, Ingrid S Gribbestad4 email and Tone F Bathen4 email

1Department of Medical Physics, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway

2Faculty of Health, Buskerud University College, 3007 Drammen, Norway

3Department of Radiation Biology, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway

4Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), 7489 Trondheim, Norway

5Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), 7489 Trondheim, Norway

6Department of Surgical Oncology, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway

7Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway

8University of Oslo, 0316 Oslo, Norway

9Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway

author email corresponding author email

Molecular Cancer 2008, 7:33doi:10.1186/1476-4598-7-33

Published: 25 April 2008

Abstract

Background

This 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.

Methods

HR 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 conclusion

HR 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.


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