Underexpression of HOXA11 is associated with treatment resistance and poor prognosis in glioblastoma

Young Bem Se, Seung Hyun Kim, Ji Young Kim, Ja Eun Kim, Yun Sik Dho, Jin Wook Kim, Yong Hwy Kim, Hyun Goo Woo, Se Hyuk Kim, Shin-Hyuk Kang, Hak Jae Kim, Tae Min Kim, Soon Tae Lee, Seung Hong Choi, Sung Hye Park, Il Han Kim, Dong Gyu Kim, Chul Kee Park

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance. Materials and Methods The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis. Results The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in those with low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified. Conclusion The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Original languageEnglish
Pages (from-to)387-398
Number of pages12
JournalCancer Research and Treatment
Volume49
Issue number2
DOIs
Publication statusPublished - 2017 Apr 1

Keywords

  • Glioblastoma
  • Homeobox genes
  • HOXA11
  • Treatment resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Se, Y. B., Kim, S. H., Kim, J. Y., Kim, J. E., Dho, Y. S., Kim, J. W., Kim, Y. H., Woo, H. G., Kim, S. H., Kang, S-H., Kim, H. J., Kim, T. M., Lee, S. T., Choi, S. H., Park, S. H., Kim, I. H., Kim, D. G., & Park, C. K. (2017). Underexpression of HOXA11 is associated with treatment resistance and poor prognosis in glioblastoma. Cancer Research and Treatment, 49(2), 387-398. https://doi.org/10.4143/crt.2016.106