Detektion relevanter Moleküle zur Diagnostik des Harnblasenkarzinoms mittels MALDI imaging

Bladder cancer is one of the most common cancer worldwide, containing a heterogeneous group of diseases with very different clinical outcomes. Until today there are no reliable biomarkers, which could have been established for early diagnosis, follow- up care or patient management in clinical routine practice. This work focuses on the technique of MALDI imaging. Compared to other proteomic tools MALDI imaging is a potential new technique providing higher sensitivity and specificity comparing and classifying fresh frozen tissue biopsies of bladder cancer. Using MALDI imaging different protein patterns could be identified, which can clearly distinguish between different tumor stages as well as between cancerous and non- cancerous tissue. Based on this classification we could generate detailed molecular images of tissue samples using FlexImaging software. These images show high congruence with H&E stained sections of the same tissue samples. With a sensitivity of 98% and a specificity of 100% cancerous tissue could be distinguished from non cancerous tissues, which outgoes sensitivity and specificity provided by other proteomic methods. Single proteins, which were detected and used to discriminate between cancerous and non cancerous tissues in other clinical studies, could be approved by this study because they achieved high priority in algorithms generated by the software. Based on these results using MALDI imaging potential biomarkers could be identified and used for establishing new clinical tests. In this context it remains to be proved if those marker proteins are detectable with high sensitivity and specificity also in urine or blood and therefore used for clinical screening tests providing early diagnosis of bladder cancer without being invasive. In order to make FFPE tissues accessible to analysis by MALDI imaging as well, we also compared different strategies of antigen retrieval. Compared to the analysis of fresh frozen tissue non of these approaches could lead to satisfying results. Antigen retrieval using trypsin digestion seems to be the most promising technique because there are few studies describing successful analysis of FFPE tissues by MALDI imaging after trypsin digestion. This method leads to other problems however, because after trypsin digestion only fragmented peptides instead of intact proteins can be detected. Therefore on the one hand this technique needs to be improved and on the other hand other strategies of antigen retrieval are still of scientific interest.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Schaumann, Katharina Elisabeth

Contributors dc:contributor

• Knüchel-Clarke, Ruth

• info:eu-repo/classification/ddc/610
• Urothel
• Krebs <Medizin>
• Matrix-unterstützte Laser-Desorption
• Proteomanalyse
• Blasentumor
• Medizin
• formalin-fixiertes Gewebe
• paraffin-eingebettetes Gewebe
• FFPE
• Antigendemaskierung
• bladder cancer
• MALDI imaging
• proteomics

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113339%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50813