Biomedical Engineering Reference
In-Depth Information
Table 2 Cancer biomarkers
Marker Type Source Cancer type Threshold References
HER2/neu Protein Serum, tissue Breast 15 ng/ml [ 111 , 112 ]
PSA Glycoprotein Serum Prostate 4 ng/ml [ 7 ]
Breast 1 pg/ml [ 113 ]
CEA Glycoprotein Serum Colon 3 ng/ml [ 7 , 111 ]
hCG Glycoprotein Serum, urine Testicular, ovarian 5 IU/l [ 7 , 111 ]
HER2 human epidermal growth factor receptor 2, PSA prostate-specific antigen, CEA carcino-
embryonic antigen, hCG human chorionic gonadotropin
consisting of 30-100 biomarkers [ 83 ]. This rough estimation of the required
number of biomarkers results from the fact that these marker profiles have not been
established yet and are still under investigation [ 1 , 4 ]. Still, a great number of
biomarkers have already been linked to cancer types, which leads to enhanced
diagnostic information than obtained using the TNM system only [ 3 , 111 ].
Currently, clinical, quantitative detection of tumor markers is typically performed
by means of immunoassay based methods [ 7 ]. Considering reduced time and
effort, biosensors could offer an alternative, provided that the demands resulting
from the respective diagnostic application are met. This means that the biomarkers
have to be detected in clinically relevant concentrations in real samples.
Furthermore, the determination of multiple concentrations in one measurement
cycle would be preferable. In the following, examples of the current state of
biosensor detection of cancer biomarkers will be shown. The biosensors presented
are immunosensors, i.e., antibodies were immobilized as analyte-specific biorec-
ognition elements on the transducer surfaces. The cancer biomarkers chosen are
listed in Table 2 , including the properties required because of the respective
diagnostic application. The biomarkers chosen are FDA-approved [ 111 ].
3.3.2 Cancer Biomarkers in Serum
Human Epidermal Growth Factor Receptor 2
Breast cancer is the most common cancer among women worldwide. Human
epidermal growth factor receptor 2 (HER2)/neu, an epithelial transmembrane
protein, is mainly regarded as prognostic or as a therapy-predictive marker for this
type of cancer [ 114 ]. The extracellular domain of HER2/neu is shed from cancer
cells into the circulation and is therefore measurable in serum. Critical values for
HER2/neu are above 15 ng/ml [ 112 ].
Immunosensors for direct and label-free detection of the HER2 extracellular
domain in serum samples were recently reported. For detection by optofluidic ring
resonators, serum samples were spiked with HER2 biomarker. The device was
able to detect HER2 concentrations in serum in the range 13-100 ng/ml [ 112 ].
For detection by means of microcantilevers, diluted patient samples were used
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