Akut Miyeloblastik Lösemilerde Gen Temelli Kanser Biyobelirteçlerin Tespiti Aracılığıyla İlaç Duyarlılığı Altgruplarının Belirlenmesi ve Prognoz Ve Tedaviye Cevabın Öngörülmesi

Abstract

The aim of this study is to determine the gene-based homogeneous subgroups of acute myeloblastic leukemias using the gene expression profiles of renin angiotensin system, the determination of biomarker potentially genes through the association of identified subgroups with clinical drugs and the prediction of prognosis and response to treatment. The Cancer Genom Project (CGP) database from Welcome Trust Sanger and the 6-Model IC50 calculation method have been used. Etoposide and doxorubicin were found to be the most effective chemotherapeutic drugs for homogenous subgroups. Three important potentially biomarker genes IGF2R, CTSA and ATP6AP2 were identified to predict the patient prognosis and response to treatment. When combined together it was found that genes were better prognostic predictors and IGF2R and CTSA were good prognostic and ATP6AP2 was poor prognostic gene. It has been demonstrated that IGF2R and CTSA can contribute to cell sensitivity by mediating autophagy and ATP6AP2 may contribute to cell resistance associated with resistance mechanisms such as TGF-. This gene panel would be useful for clinicians during pretreatment evaluation for determination of appropriate and effective chemotherapoetic agent for the patient. Before starting treatment, this gene panel could make the prediction of patient prognosis and it directs clinicians to the effective treatments. In our study, an exemplary and original approach to how a large database can be used for the detection of a suitable chemotherapeutic agent and biomarker gene for a particular type of cancer has been described.