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Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival.

ABSTRACT: BACKGROUND:Cancer cachexia is a complex wasting syndrome affecting patients with advanced cancer, with systemic inflammation as a key component in pathogenesis. Protein degradation and release of amino acids (AAs) in skeletal muscle are stimulated in cachexia. Here, we define factors contributing to serum AA levels in colorectal cancer (CRC). METHODS:Serum levels of nine AAs were characterised in 336 CRC patients and their relationships with 20 markers of systemic inflammatory reaction, clinicopathological features of cancers and patient survival were analysed. RESULTS:Low serum glutamine and histidine levels and high phenylalanine levels associated with indicators of systemic inflammation, including high modified Glasgow Prognostic Score, high blood neutrophil/lymphocyte ratio and high serum levels of CRP, IL-6 and IL-8. Low levels of serum glutamine, histidine, alanine and high glycine levels also associated with advanced cancer stage and with poor cancer-specific survival in univariate analysis. CONCLUSIONS:In CRC, serum AA levels are associated with systemic inflammation and disease stage. These findings may reflect muscle catabolism induced by systemic inflammation in CRC.

SUBMITTER: Sirnio P

PROVIDER: S-EPMC6342921 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival.

Sirniö Päivi P Väyrynen Juha P JP Klintrup Kai K Mäkelä Jyrki J Karhu Toni T Herzig Karl-Heinz KH Minkkinen Ilkka I Mäkinen Markus J MJ Karttunen Tuomo J TJ Tuomisto Anne A

British journal of cancer 20181219 2

<h4>Background</h4>Cancer cachexia is a complex wasting syndrome affecting patients with advanced cancer, with systemic inflammation as a key component in pathogenesis. Protein degradation and release of amino acids (AAs) in skeletal muscle are stimulated in cachexia. Here, we define factors contributing to serum AA levels in colorectal cancer (CRC).<h4>Methods</h4>Serum levels of nine AAs were characterised in 336 CRC patients and their relationships with 20 markers of systemic inflammatory rea ...[more]

PMID: 30563990

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Project description:BACKGROUND: Presently, 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. METHODS: Sera 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). RESULTS: The 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). CONCLUSIONS: In 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.

Dataset Information

Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival.

Publications

Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival.

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