4 research outputs found
Colon cancer : Disease related proteins in tumor tissue and serum
Despite the progress in surgical techniques and adjuvant therapies the
mortality of around 60% within the group of colon cancer patients did not
decrease significantly over the last decades. This determines a growing
demand for biomarkers for early detection, prognosis and risk assessment
in colorectal malignancies. Desirable criteria for such a biomarker test
are minimal burden and maximum safety for the patient, cost efficiency
and broad acceptance to reach a high compliance of the patients.
More than 300 colon tissue samples and 1000 sera were obtained from CRC
and FAP patients at the Lübeck and Düsseldorf University Hospitals in
Germany. To identify the consequences of genetic aberrations on protein
expression level, samples from patients with advanced sporadic colon
cancers in which the corresponding mucosa, adenoma, carcinoma and liver
metastasis were available, were analyzed by 2-D gel electrophoresis and
mass spectrometry. A total of 46 proteins were found to be upregulated
during the progression of sporadic cancer, and 26 were downregulated.
Several of the identified polypeptides correlate with proteins regulating
specific cell functions (cell cycle, cytoskeleton, metabolic pathways).
In a further study we used a 2-DE based proteomic approach to compare the
expression pattern of normal colonic mucosa vs. mucosa gained from FAP
patients, polyps vs. FAP polyps and sporadic vs. FAP associated cancer,
respectively. A total of 47 proteins were always present in FAP mucosa
and absent in the normal mucosa. Based on a total of 37 proteins FAP
polyps and sporadic polyps could be distinctly separated. In addition,
the absence/presence pattern of 66 spots allowed to distinguish FAP
cancers from sporadic cancers. These data suggest, that proteome analysis
makes it possible to diagnose FAP already on macroscopically normal
appearing colonic mucosa. By means of SELDI array based investigations we
unrevealed 16 serum proteins that were able to classify 98% of all test
set samples correctly. Our SELDI results show that serum marker protein
profiling enables to diagnose and discern malignant colon cancer patients
from healthy individuals. Although these markers need validation before
they can be used in clinics they have potential for the design of a
marker panel for objective diagnosis and therapeutic strategies for
colorectal cancer and metastasis