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Abstract

Transcriptomic Alterations Induced By Vemurafenib after Treatment of Melanoma: A Comprehensive Bioinformatics Analysis

Author(s): J. Xie, Y. Cao, Z. Zhu, S. Ruan, M. Wang and J. Shi*
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, 1The Forth School of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Correspondence Address:
J. Shi, Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China


Melanoma is a highly aggressive kind of cancer with a very poor prognosis. v-Raf murine sarcoma viral oncogene homolog B1 inhibitor vemurafenib has indeed harvested substantial clinical benefits. Nevertheless, its drug resistance has also hampered scientists’ efforts towards successful melanoma treatment. In this study, we used data derived from the gene expression omnibus database to analyze the effect on vemurafenib sensitive cell lines after vemurafenib treatment. Gene expression omnibus datasets GSE42872 (cohort 1), GSE127988 (cohort 2), GSE110054 (cohort 3) were included in the analysis. We found 25 common differentially expressed genes in 3 datasets, including 10 upregulated genes and 15 downregulated genes after vemurafenib application. Analysis using web tool Timer showed a significant correlation of the upregulated genes with immune infiltration level in skin cell melanoma. Gene ontology enrichment analysis showed that after vemurafenib treatment, all datasets showed downregulation in deoxyribonucleic acid replication and cell cycle arrest. Meanwhile, genes related to neurogeneration, extracellular matrix and cell-cell adhesion were significantly enriched in all three datasets. Kyoto Encyclopedia of Genes and Genomes analysis showed that pathways like P53, phosphatidylinositol 3-kinase-protein kinase B and Ras-associated protein signaling pathways were enriched in differentially expressed genes after vemurafenib administration. The findings of the candidate differentially expressed genes and pathways may not only reveal the cellular sensitivity to vemurafenib treatment but also give rise to a better understanding of the mechanism of cancer cell cycle arrest and cellular resistance towards vemurafenib targeted therapy.

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Citations : 53647

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