방사선의학 웹진

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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 5 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 radio-sensitizers. 

Author information

Se YB1, Kim SH2, Kim JY1, Kim JE1, Dho YS1, Kim JW1, Kim YH1, Woo HG3, Kim SH4, Kang SH5, Kim HJ6, Kim TM7, Lee ST8, Choi SH9, Park SH10, Kim IH6, Kim DG1,2, Park CK1,2.​

1Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

2Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

3Department of Physiology, Ajou University School of Medicine, Suwon, Korea.

4Department of Neurosurgery, Ajou University School of Medicine, Suwon, Korea.

5Department of Neurosurgery, Korea University College of Medicine, Seoul, Korea.

6Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

7Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

8Department of Neurology, Seoul National University Hospital, Seoul, Korea.

9Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

10Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.