Objective: The renin angiotensin system (RAS) is a prognostic molecular target for a large cancer group and plays an essential role in cancer biology. This critical system affects tumor growth and spread, both directly and indirectly, including endometrial cancer (EC). RAS activation has been strongly associated with the expression of angiogenesis, metastasis, and pro-angiogenic factors. The aim of this study was to identify EC subgroups according to variations in RAS genes and evaluate the prediction of chemotherapy resistance.
Materials and Methods: Hierarchical clustering, variance, t-test, fold change, false discovery rate calculation, and geneset enrichment analyses were performed using microarray and drug sensitivity data obtained from the Genomics of Drug Sensitivity in Cancer Project database and the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress (accession no: E-MTAB-783).
Results: Subgroups of endometrial cancer cell lines were determined based on the RAS gene family. These subgroups were asso-ciated with 2 critical chemotherapeutic agents: vinblastine and epothilone B. Important gene sets were identified in the subgroups.
Conclusion: Pharmacological effects of RAS genes may differ in EC cells, depending on the pathological behavior of genomic subtypes. The results of this study showed that RAS genes were potential biomarkers for drug sensitivity and prog-nosis of endometrial cancer. RAS and NOTCH/autophagosome pathways may be related in EC. If the data of this study are confirmed by in vitro experiments and clinical samples, RAS genes would seem to be robust prognostic biomarkers for vinblastine and epothilone B.