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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 387 - 398 (12page)
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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.
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참고문헌 (52)
참고문헌 신청
De Vita G / 1993 / Expression of homeobox-containing genes in primary and metastatic colorectal cancer / Eur J Cancer 29:887~893
Costa BM / 2010 / Reversing HOXA9 oncogene activation by PI3K inhibition : epigenetic mechanism and prognostic significance in human glioblastoma / Cancer Res 70:453~462
Lim JY / 2013 / Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype / World J Gastroenterol 19:7078~7088
Carrio M / 2005 / Homeobox D10induces phenotypic reversion of breast tumor cells in a threedimensional culture model / Cancer Res 65:7177~7185
Petrini M / 2013 / HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line / Cancer Cell Int 13:101
Costa BM / 2010 / Reversing HOXA9 oncogene activation by PI3K inhibition : epigenetic mechanism and prognostic significance in human glioblastoma / Cancer Res 70:453~462
Lim JY / 2013 / Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype / World J Gastroenterol 19:7078~7088
Carrio M / 2005 / Homeobox D10induces phenotypic reversion of breast tumor cells in a threedimensional culture model / Cancer Res 65:7177~7185
Petrini M / 2013 / HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line / Cancer Cell Int 13:101
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