Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis

Shojaei, Mona
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data of each cancer cell line (as control) was compared to “sorafenib” and “PI3K/Akt Pathway inhibitors” treated data. Somatic mutations associated with drug resistance were comparatively identified with MuTect tool. The results were then filtered to distinguish the missense mutations. The common genes among drug-resistant sets were found to be associated with liver cancer perseverance and aggressiveness. SLC39A5, FRG1, PPHLN1 and SRP9 gene mutations were found to be the most significant, shared among three drug treated sets. The sets were further investigated in detail to discover the liver cancer associated survival genes. Using our results, appropriate targets can be defined that play critical roles in cancerous cell growth for drug development purposes. 


Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients
Kaya, P; Gündüz, Ufuk; Arpaci, F; Ural, AU; Guran, S (2005-09-01)
Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein e...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Mutlu, Pelin; Pourianazar, Negar Taghavi; Yucel, Meral; Gündüz, Ufuk (2018-01-01)
Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of beta-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR...
Training of ANFIS Network by Genetic Algorithm for Diagnosis of Leukemia Cancer Subtypes Using Gene Expression Profile
Arslan, Mustafa Turan; Haznedar, Bülent; Kalınlı, Adem (2017-05-12)
In this study, subtypes of Leukemia cancer has classified by using microarray gene expression profiles. An approach is proposed to train Adaptive Neuro Fuzzy Inference System (ANFIS) network by using a population-based Genetic Algorithm (GA) to classify this cancer data. The classification success of the proposed model has compared with the successes of Backpropagation (BP)-ANFIS and Hybrid-ANFIS, which are derivative based ANFIS models. According to obtained results, GA-ANFIS model has performed ve...
Identification of Potential Therapeutic Genes and Pathways in Phytoestrogen Emodin Treated Breast Cancer Cell Lines via Network Biology Approaches
Sakalli-Tecim, Elif; Uyar-Arpaci, Pembegul; Güray, Nülüfer Tülün (2021-02-01)
Phytoestrogens have been investigated for their potential anti-tumorigenic effects in various cancers including breast cancer. Emodin being a phytoestrogen shows anti-carcinogenic properties especially in estrogen receptor positive (ER+) breast cancers. The aim of this study is to identify the molecular mechanism and related biological pathways in both (ER+) MCF-7 and (ER-) MDA-MB-231 breast cancer cell lines upon Emodin treatment via microarray analysis in order to find out therapeutic biomarkers. In both ...
Citation Formats
M. Shojaei, “Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis,” M.S. - Master of Science, Middle East Technical University, 2016.