Z Gastroenterol 2015; 53 - V01
DOI: 10.1055/s-0035-1551683

Dimethylarginine serum concentrations effectively identify subjects with colorectal carcinoma

SK Eder 1, TK Felder 2, A Stadlmayr 3, U Huber-Schönauer 4, D Niederseer 3, W Patsch 5, E Aigner 1, C Datz 3
  • 1First Department of Medicine, Paracelsus Medical University, Salzburg, Austria
  • 2Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
  • 3Department of Internal Medicine, General Hospital, Oberndorf, Austria
  • 4Department of Laboratory Medicine, General Hospital, Oberndorf, Austria
  • 5Department of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria

Background and Aims:

Along the progression from normal colonic mucosa to colorectal cancer systemic metabolic pathways may be affected. We aimed to identify metabolic features and possible biomarkers of colorectal carcinoma and advanced adenoma.

Methods:

According to the results of screening colonoscopy 402 patients were allocated to one of 3 groups: colorectal carcinoma (CRC, n = 47), advanced adenoma (AA, n = 55), control (CTRL, n = 300). The serum metabolite profile of all subjects was obtained by API 4000 triple quadrupole mass spectrometer (ABSciex) using the AbsoluteIDQTM p180 kit (BIOCRATES Life Sciences). Significant differences in metabolomics analyses were determined by Significance Analysis of Microarrays (SAM) using false discovery rate (FDR).

Results:

The metabolite profile of CRC was markedly different from the other two groups while AA und CTRL were found to largely overlap.

In particular, CRC showed significantly higher levels of total dimethylarginine (TDMA), acyl carnitines C16, C16-OH, C16:1, C16:1-OH, C16:2, sphingomyelin (SM) C22:3 and SM C20:2 (FDR < 0.001).

For differentiation between CRC and subjects without carcinoma biomarker analysis based on Receiver Operating Characteristic (ROC) was conducted. For TDMA an area under the curve (AUC) of 0.92 was found.

Apart from TDMA, combining the other above mentioned metabolites an AUC of 0.879 and combining the most significant, in particular TDMA, SM 22:3 and C16-OH, an AUC of 0.950 was obtained for distinguishing CRC from AA/CTRL. AA and CTRL could be separated by concentrations of the amino acids glutamine, valine and serine (AUC 0.816).

Conclusions:

TDMA serum concentrations may serve as a potential biomarker for the identification of colorectal carcinoma. Its role in colon carcinogenesis needs to be investigated further.