Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection.

BMC Med 2010 Feb 15;8:13. Epub 2010 Feb 15.

Phenomenome Discoveries Inc, Saskatoon, SK, Canada.

Background: There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.

Methods: Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220).

Results: Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 +/- 0.04).

Conclusions: A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.

Download full-text PDF

Source
http://dx.doi.org/10.1186/1741-7015-8-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833138PMC
February 2010

Publication Analysis

Top Keywords

crc patients
12
hydroxylated polyunsaturated
12
independent populations
12
crc
9
three independent
8
colorectal cancer
8
biomarkers independent
8
japan total
8
metabolomics technology
8
tq-mrm method
8
usa japan
8
reduced levels
8
polyunsaturated ultra
8
ultra long-chain
8
independent
5
three
5
independent cohorts
4
metabolomic analyses
4
cohorts crc
4
patient samples
4

Similar Publications

Metabolic system alterations in pancreatic cancer patient serum: potential for early detection.

BMC Cancer 2013 Sep 12;13:416. Epub 2013 Sep 12.

Phenomenome Discoveries, Inc,, Saskatoon, SK, Canada.

Background: The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. Read More

View Article and Full-Text PDF
September 2013

Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age.

BMC Gastroenterol 2010 Nov 29;10:140. Epub 2010 Nov 29.

Phenomenome Discoveries Inc, Saskatoon, Saskatchewan, Canada.

Background: Serum levels of novel hydroxy polyunsaturated ultra long-chain fatty acids (hPULCFAs) have been previously shown to be reduced in pre-treatment CRC patients compared to disease-free subjects, independent of disease stage. However, whether reduced levels of hPULCFAs result from the presence of cancer is currently unknown, as is the distribution of hPULCFAs in the general population. The following studies were carried out to assess whether conventional therapy would result in restoration of systemic hPULCFAs in CRC patients, and to investigate the relationship between hPULCFA levels and age. Read More

View Article and Full-Text PDF
November 2010

[Metabolome Analysis of Human Serum: Implications for Early Detection of Colorectal Cancer].

Authors:
Yasuyo Yamazaki

Rinsho Byori 2015 Mar;63(3):328-35

With the recent development of novel technologies capable of comprehensively detecting and accurately identifying small molecules within biological samples--the field of metabolomics--new information about disease biology is emerging. A comprehensive metabolomics strategy was used to discover novel small molecules which were significantly decreased in the serum of colorectal cancer (CRC) patients relative to normal individuals. The metabolite markers, hydroxylated polyunsaturated ultra long-chain fatty acids (hPULCFAs), were characterized using HPLC-coupled tandem mass spectrometry, and a high-throughput screening (HTS) method compatible with conventional triple-quadrupole mass spectrometers in clinical labs. Read More

View Article and Full-Text PDF
March 2015

High-throughput and high-sensitivity quantitative analysis of serum unsaturated fatty acids by chip-based nanoelectrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry: early stage diagnostic biomarkers of pancreatic cancer.

Analyst 2014 Apr;139(7):1697-706

Department of Biophysics and structural biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dongdan San Tiao, Beijing 100005, PR China.

In this study, Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) coupled with chip-based direct-infusion nanoelectrospray ionization source (CBDInanoESI) in a negative ion mode is first employed to evaluate the effect of serum and its corresponding supernatant matrixes on the recoveries of serum free fatty acids (FFAs) based on spike-and-recovery experimental strategy by adding analytes along with analog internal standard (IS). The recoveries between serum (69.8-115. Read More

View Article and Full-Text PDF
April 2014