Filtering of the Gene Signature as the Predictors of Cisplatin-Resistance in Ovarian Cancer

Document Type : Research Paper

Authors

1 Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia

2 Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

3 Department of Molecular medicine, Pasteur Institute of Iran, Tehran, Iran

4 Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.

Abstract

Background: Gene expression profiling and prediction of drug responses based on the molecular signature indicate new molecular biomarkers which help to find the most effective drugs according to the tumor characteristics.
Objectives: In this study two independent datasets, GSE28646 and GSE15372 were subjected to meta-analysis based on Affymetrix microarrays.
Material and Methods: In-silico methods were used to determine differentially expressed genes (DEGs) in the previously reported sensitive and resistant A2780 cell lines to Cisplatin. Gene Fuzzy Scoring (GFS) and Principle Component Analysis (PCA) were then used to eliminate batch effects and reduce data dimension, respectively. Moreover, SVM method was performed to classify sensitive and resistant data samples. Furthermore, Wilcoxon Rank sum test was performed to determine DEGs. Following the selection of drug resistance markers, several networks including transcription factor-target regulatory network and miRNA-target network were constructed and Differential correlation analysis was performed on these networks.
Results: The trained SVM successfully classified sensitive and resistant data samples. Moreover, Performing DiffCorr analysis on the sensitive and resistant samples resulted in detection of 27 and 25 significant (with correlation ≥|0.9|) pairs of genes that respectively correspond to newly constructed correlations and loss of correlations in the resistant samples.
Conclusions: Our results indicated the functional genes and networks in Cisplatin resistance of ovarian cancer cells and support the importance of differential expression studies in ovarian cancer chemotherapeutic agent responsiveness.

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