Identification of gene mutations ınvolved in drug resistance in liver cancer using rna-seq data analysis

2017-06-28
Shojeai, Mona
Akhan, Ece
Acar, Aybar Can
Atalay, Rengül
Cancer is the leading cause of death worldwide and the risk increases with aging. A significant concern in cancer research is the detection of cancer drug resistance associated somatic mutations. According to Global Cancer Statistics (GCS) liver cancer is the 5th most common and 2nd deadliest cancer in the world. Over the past two decades, the death rate for liver cancer increased by 2.5% per year and incidents were 3 times higher in men than in women (American Cancer Society). Appropriate treatment of hepatocellular carcinoma (HCC, primary liver cancer) depends on the disease stage, patient’s age and overall health and individual priorities. Targeted therapies are known to block cancer-associated proteins or prevent cell proliferation and invasion. Unlike conventional chemotherapy, which affects the whole normal and cancerous fast-growing cells, targeted drugs attack specific molecules in cancer cells and have much less impact on healthy tissues. With targeted therapy in mind, 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 samples. Somatic mutations associated with drug resistance were comparatively identified with MuTect tool (Cibulskis, 2013). The results were then filtered to distinguish the missense mutations. The common genes among drugresistant 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. Drugs with specific targets can find the appointed place and turn the target gene off to disturb the cancer cells’ proliferation. Accordingly, the mutated genes activities are stopped and the disease progression is prevented. The mutated genes that we identified during the chemical knockdown studies can be further studied in gene expression vs. patient survival data. These genes are being analyzed in laboratory to test whether their silence (knocking-down founded gene mutations which are correlated with liver cancer under drug treatments) decreases cancer growth or not. In our success we can target these genes in future cancer treatments. Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnology (2013).doi:10.1038/nbt.2514
Citation Formats
M. Shojeai, E. Akhan, A. C. Acar, and R. Atalay, “Identification of gene mutations ınvolved in drug resistance in liver cancer using rna-seq data analysis ,” presented at the 10th International Symposium on Health Informatics and Bioinformatics, June 28– 30 2017, Güzelyurt, Northern Cyprus, 2017, Accessed: 00, 2021. [Online]. Available: http://hibit2017.ii.metu.edu.tr/wordpress/wp-content/uploads/HIBIT2017_Conference_Book.pdf.