Medizinische Universität Graz - Research portal
Selected Publication:
Mach, M.
Identification of prognostic methylation markers in stage II colorectal cancer patients.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2013. pp.65.
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- Authors Med Uni Graz:
- Advisor:
- Heitzer Ellen
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- Abstract:
- Surgical excision is still the gold standard in treatment of patients with colorectal cancer (CRC), since it is the most effective treatment especially in stages I and II. Generally, the overall survival (OS) and disease free survival (DFS) rate of patients with stage II colon cancer is quite good. So far no suitable molecular markers are available to identify high-risk patients that would benefit from adjuvant chemotherapy. Promoter hypermethylation is known to play an important role in cancer development and might therefore provide a biomarker for a more accurate estimation of recurrence risk. The focus of this thesis was the identification of new prognostic markers to facilitate the decision for therapy management in patients with stage II colorectal cancer. Furthermore, the suitability of the established MethyLight assays for the identified biomarkers was analyzed in free circulating DNA, in order to provide a non-invasive test. A total of 154 tumor samples of patients with stage II CRC were investigated with regard to the methylation status. The patient collective was postoperatively assigned to either treatment with 5-Fluorouracil or surveillance only and analyzed in order to elucidate the correlation between methylation status, OS, and DFS. We were able to identify the methylation status of promoter regions of SPARC, UCHL1, and PCDH10 as prognostic markers for patients with CRC. Patients of the surveillance group had a significantly prolonged OS and DFS when they were methylated in the respective promoter sites. In contrast, patients who were methylated and received chemotherapy did not benefit from the treatment. In conclusion, the methylation status of our identified markers might give good predictive evidence for therapy decisions. If patients were methylated, chemotherapy should not be applied, since they were likely to have a poor prognosis by the application of pharmaceutical agents, and presented a