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.
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.


CONCLUSIONS
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.
Seierstad
Therese
T
Department of Medical Physics, Rikshospitalet-Radiumhospitalet Medical Center, 0310 Oslo, Norway. therese@radium.uio.no
Røe
Kathrine
K
Sitter
Beathe
B
Halgunset
Jostein
J
Flatmark
Kjersti
K
Ree
Anne H
AH
Olsen
Dag Rune
DR
Gribbestad
Ingrid S
IS
Bathen
Tone F
TF
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D025341:Principal Component Analysis / Q000379:methods*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D013113:Spin Labels; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D013113:Spin Labels