Serum metabolomic profile as a means to distinguish stage of colorectal cancer

Abstract

BackgroundPresently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.MethodsSera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25).ResultsThe serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5).ConclusionsIn CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

“…In this review, there was evidence that metabolite modulation was discernable at very early stages of GI cancer (30,46,52,(57)(58)(59). Several studies reported incremental metabolomic changes with invasive (41,43,58,59) and metastatic (46,70,71) progression. In addition, three studies in colorectal cancer that were excluded from the appraisal process owing to their design nonetheless demonstrated pertinent findings to metabolomic dynamics.…”

Metabolomic Profiling in Colorectal Cancer: Opportunities for Personalized Medicine

“…Farshidfar et al performed a serum metabolomic profile to distinguish different stages of CRC patients among locoregional CRC, hepatic-specific metastases and extrahepatic metastases, which revealed that the metabolome changed markedly for the different stages [75]. Such metabolic changes were due to the difference in tumor biology as well as the site-specific host response to the tumor.…”

NMR-Spektroskopie – ein modernes Werkzeug zur Serum-Analytik von Lipoproteinen und Metaboliten

“…Unterschiedliche Konzentrationen von Aminosäuren und Zuckern ließen auf einen gestörten Energiestoffwechsel schließen, d.h. Lipolyse, Krebszyklus und Aminosäure-Abbau. In einer Studie an 103 Patienten mit kolorektalem Adenokarzinom -davon 42 mit lokoregionärem Karzinom, 45 mit Lebermetastasen und 25 auch mit extrahepatischen Metastasen -konnte man außerdem eindeutig zwischen den verschiedenen Gruppen mittels NMR-Spektroskopie oder Gaschromatographie unterscheiden [76]. Diese Ergebnisse zeigen die universelle Einsetzbarkeit der NMR in der Krebsforschung, was zu neuen Erkenntnissen über gestörte Stoffwechselprozesse führt.…”