In a recent study published in PLOS ONE, Broker et al. (2013) describe an innovative method for detecting metastasis of colorectal cancer to the liver.1 With a larger sample size, this study could provide evidence for a less invasive and less expensive diagnostic tool for follow-up colorectal cancer patients.
Colorectal cancer is the third-largest cause of death from cancer; two-thirds of all colorectal cancer deaths are the result of liver metastasis.2 A series of blood tests monitoring carcinoembryonic antigen is a standard of care for follow-up of patients treated for colorectal cancer. Studies have shown, however, that although post-operative carcinoembryonic antigen elevation indicates recurrence with high probability, the sensitivity and accuracy of the tests are not as high as one may hope.3 In addition to this, low follow-up completion rates have been noted; this, in turn, impacts the long-term survival rates of patients.
Broker et al. focused on the urine proteome to develop a diagnostic tool for colorectal cancer metastasis to the liver. The urine proteome is able to provide detailed information for monitoring changes in physiology, and its collection is non-invasive. The authors demonstrate that it is possible to differentiate among liver tumors using urine; they have validated naturally occurring peptides that distinguish between healthy patients and those with metastasis.
The authors measured urine samples using nano liquid chromatography coupled online to an LTQ Orbitrap XL (Thermo Scientific). Following validation, the authors identified seven collagen peptides that differed between control patients and colorectal liver metastasis. Two promising peptides stood out for further evaluation — AGPP(-OH)GEAGK P(-OH)GEQGV P(-OH)GDLGA P(-OH)GP and KGNSGE P(-OH)GAPGSKGDTGAKGE P(-OH)GPVG. Both peptides are part of collagen 1, which is abundant in the extracellular matrix in the adult liver, a known site for remodeling during invasion.
Most importantly, the researchers found that the sensitivity and specificity of these peptides for colorectal liver metastasis were 88% and 89%, respectively — and, when retested in the Orbitrap, sensitivity and specificity were at 60.2% and 84.6% in the validation model.
With further validation, urine proteomics may prove a more economical, more effective and less invasive method for colorectal cancer patient follow-up. In turn, this could lead to significant improvements in quality of life and survivorship.
1. Broker, M.M.E. (2013, August) “Collagen peptides in urine: A new promising biomarker for the detection of colorectal liver metastases,” PLOS ONE, 8(8) (e70918), doi: 10.1371/journal.pone.0070918.
2. Stangl, R. (1994) “Factors influencing the natural history of colorectal liver metastases,” Lancet, 343(8910) (pp.1405–10).
3. Hara, M. (2008) “Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: Analysis with likelihood ratio and post-test probability in a follow-up study,” Diseases of the Colon and Rectum, 51(11) (pp. 1675–80), doi: 10.1007/s10350-008-9406-1.
Post Author: Miriam Pollak. Miriam specialised in neuroscience as an undergraduate but traded in lab work for a post graduate degree in science communication.
She has since had a career that has spanned science communication, science education and communications management.
However, Miriam has found her bliss balancing her love of writing and disseminating medical research with managing a multimillion dollar research budget for a childhood cancer charity in Australia.