Breast cancer is the most common cancer in women worldwide in both developed and developing countries.1 In higher income countries, it is the leading killer in women aged 29-55. The National Cancer Institute (NCI) estimates 229,060 new cases of breast cancer (226,870 women and 2,190 men) diagnosed in 2012 and 39,920 deaths (39,510 women and 410 men) from breast cancer will occur.1,2,3
There is a need to delve into biomarker cancer research, specific to each cancer, to detect the disease in early stages in a fast and sensitive manner. The use of noninvasive techniques to acquire samples from patients is preferable, such as urine or plasma, which can be obtained in large quantities.5 Biomarker cancer research on bodily fluids is ideal as it is non-invasive. However, fluids such as plasma also carry a high concentration of circulating proteins, which can interfere with the low concentration of biomarker proteins.4,5
In the case of breast cancer, there is a genetic predisposition towards the disease, which would allow for genetic testing; however, the remaining factors are environmental and include obesity, low fruit and vegetable consumption, lack of physical activity, and alcohol.3,6
Suh et al. from the BRI Korea Institute of Science and Technology have been focusing on the idea that proteins can be used for biomarker cancer research and are working on identifying known breast cancer biomarkers in plasma. Initial optimization was performed using six patients with breast cancer and six healthy individuals. The resulting method was then validated using 30 healthy patients and 30 patients with breast cancer. Their method involved using a plasma depletion kit to remove IgG and albumin, followed by tryptic digest of the mixtures and labelling the tryptic peptides with either a light chain (healthy) or a heavy chain (breast cancer). The samples were mixed together and separated and sequenced using LC-MS/MS on a LTQ XL Orbitrap (Thermo Scientific). Using the relative abundance of the peptides to identify changes in levels of protein concentration, two proteins that had at least a 2-fold increase in breast cancer patients were identified as potential biomarker cancer targets for screening. THBS1 (thrombospondin-1) is the first protein identified with three peptides identified at all stages of breast cancer (0-III) and was found at higher concentrations in older patients. The second protein is BRWD3 (bromodomain and WD repeat-containing protein 3), which was identified by two unique peptides and showed no clear difference with age or any or with stage of breast cancer.5
Protein biomarker cancer research is a growing field. As more is known about the disease, targeted approaches can be used to identify biomarkers. Development of instrumentation and methodology allows for rapid and sentitive identification of these target molecules. Breast cancer, in this instance, has made significant progress towards identifying a biomarker for cancer and detecting the disease in its early stages so that measures can be used to treat the disease before it becomes life threatening. Biomarker cancer research is also being re-evaluated with the idea that the use of a single biomarker per disease may not be the best approach but that the use of multiple biomarkers from one sample is feasible and gives better identification of the disease and potentially the disease state.5
References
1. National Guideline, C., (2008), ‘Guideline implementation for breast healthcare in low-income and middle-income countries’, http://guideline.gov/content.aspx?id=13344‘
3. Samphao, S., et al., (2009), ‘Diagnosis of breast cancer in women age 40 and younger: delays in diagnosis result from underuse of genetic testing and breast imaging‘, The American Journal of Surgery, 198 (4), (538-543)
4. Hale, J.E., et al., (2003), ‘Application of proteomics for discovery of protein biomarkers‘, Briefings in Functional Genomics & Proteomics, 2 (3), (185-193)
5. Suh, E.J., et al., (2012), ‘Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers‘, Experimental and Molecular Medicine, 44 (1), (36-44)
6. Danaei, G., et al., (2005), ‘Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors‘, Lancet, 366 (9499), (1784-1793)
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