Zusammenfassung
Microarrays erlauben die simultane Analyse der Expression tausender Gene und liefern so ein Expressionsprofil der untersuchten Probe. Damit ist dieses Verfahren besonders geeignet, die komplexen genetischen Veränderungen maligner Tumoren zu charakterisieren. Die Auswertung durch sog. „unbeaufsichtigte hierarchische Clusteranalysen“ zeigt, dass charakteristische Expressionsprofile für Individuen, Organe und Gewebe sowie verschiedene Zelltypen bestehen. Bei Tumoren konnten „molekulare Signaturen“ im Vergleich zum Normalgewebe für unterschiedliche Tumorstadien und Risikogruppen, aber auch für das Ansprechen auf eine bestimmte Therapie beobachtet werden.
Beim Prostatakarzinom konnten zahlreiche tumorspezifische Expressionsveränderungen identifiziert werden. Von diesen scheinen insbesondere die Zelloberflächenprotease Hepsin und die α-Methyl-Acryl-CoA-Racemase Bedeutung für die Diagnosestellung zu erlangen. Darüber hinaus wurden Genexpressionsprofile identifiziert, die mit fortgeschrittenem Tumorstadium, geringer Differenzierung oder der Progression nach radikaler Prostatektomie assozziiert sind. Eine gesteigerte Expression von Enzymen der Steroidbiosynthese sowie des Androgenrezeptors ist Teil der „molekularen Signatur“ hormonrefraktärer Prostatakarzinome.
Abstract
Microarrays allow a simultaneous gene expression analysis of thousands of genes, providing an expression profile of the specimen investigated. Thus, this procedure is well suited to characterize the complex genetic alterations of malignant tumors. Using unsupervised hierarchical cluster analysis, characteristic expression profiles for individuals, organs and tissues, as well as for different cell types, can be identified. Molecular signatures have been observed in tumors compared to normal tissue, for different tumor stages, risk groups or response therapy. In prostate cancer, many tumor-specific gene expression alterations have been identified. Among these, the cell surface protease hepsin and α-methyl-acryl-CoA-racemase might gain importance as diagnostic tools. Moreover, gene expression profiles were identified which are associated with advanced tumor stage, poor differentiation or progress after radical prostatectomy. Increased expression of enzymes of steroid biosynthesis and the androgen receptor appears to be part of the molecular signature of hormone refractory prostate cancer.
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Grimm, MO., Hartmann, F.H. & Schulz, W.A. Microarrays. Urologe [A] 43, 653–658 (2004). https://doi.org/10.1007/s00120-004-0578-6
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DOI: https://doi.org/10.1007/s00120-004-0578-6