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Systematic identification of novel biomarker signatures associated with acquired erlotinib resistance in cancer cells

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Abstract

Acquired erlotinib resistance (AER) during cancer treatment remains a major clinical challenge that results in the recurrence and metastasis of cancers. Therefore, we sought to identify differentially expressed genes (DEGs) by performing a meta-analysis of AER-related microarray datasets and discover biomarkers by conducting a systemic in-silico analysis. Using the RankProd algorithm, we identified 775 DEGs (536 up-regulated and 239 down-regulated). Functional enrichment analyses of the total DEG s suggested that “cell adhesion” and “cytokine-cytokine receptor interactions” may be closely associated with AER process. Some DEGs shared target sites of the potential micro-RNA including miR-21, miR-200b/c, miR-429 and miR-9. Target sites of FOXJ1, NFAT, FOXO4, and JUN were also significantly enriched. From the proteinprotein interaction network, we clustered four functional modules by p-value and node density and found hub genes with many interacting neighbors. Finally, we identified seven candidate hub DEGs (TIMP3, SPARC, ITGA1, CCNA1, SOX2, KRT14, and PTPRZ1) for AER development.

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Korea

    Young Seok Lee, Jin Ki Kim, Young Rae Kim, Ho Sung Myeong, Young Tae Ro, Yun Hee Noh & Sung Young Kim

  2. Department of Plastic and Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Korea

    Tae Hwan Park

  3. School of Korean Medicine, Pusan National University, Busan, Korea

    Kang Kwon

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  1. Young Seok Lee
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  2. Jin Ki Kim
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  3. Tae Hwan Park
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  4. Young Rae Kim
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Correspondence to Sung Young Kim.

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Lee, Y.S., Kim, J.K., Park, T.H. et al. Systematic identification of novel biomarker signatures associated with acquired erlotinib resistance in cancer cells. Mol. Cell. Toxicol. 12, 139–148 (2016). https://doi.org/10.1007/s13273-016-0018-x

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  • DOI: https://doi.org/10.1007/s13273-016-0018-x

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