Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients

    Access Status
    Open access via publisher
    Authors
    Candy, P.
    Phillips, M.
    Redfern, A.
    Colley, S.
    Davidson, J.
    Stuart, L.
    Wood, B.
    Zeps, Nikolajs
    Leedman, P.
    Date
    2013
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Candy, P. and Phillips, M. and Redfern, A. and Colley, S. and Davidson, J. and Stuart, L. and Wood, B. et al. 2013. Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. British Journal of Cancer. 109 (4): pp. 1023-1030.
    Source Title
    British Journal of Cancer
    DOI
    10.1038/bjc.2013.431
    ISSN
    0007-0920
    URI
    http://hdl.handle.net/20.500.11937/7948
    Collection
    • Curtin Research Publications
    Abstract

    Background: The purpose of this study was to evaluate the expression of Notch-induced transcription factors (NTFs) HEY1, HES1 and SOX9 in colorectal cancer (CRC) patients to determine their clinicopathologic and prognostic significance. Methods: Levels of HEY1, HES1 and SOX9 protein were measured by immunohistochemistry in a nonmalignant and malignant tissue microarray of 441 CRC patients, and the findings correlated with pathologic, molecular and clinical variables. Results: The NTFs HEY1, HES1 and SOX9 were overexpressed in tumours relative to colonic mucosa (OR=3.44, P<0.0001; OR=7.40, P<0.0001; OR=4.08 P<0.0001, respectively). HEY1 overexpression was a negative prognostic factor for all CRC patients (HR=1.29, P=0.023) and strongly correlated with perineural and vascular invasion and lymph node (LN) metastasis. In 5-fluorouracil (5-FU)-treated patients, the tumour overexpression of SOX9 correlated with markedly poorer survival (HR=8.72, P=0.034), but had no predictive effect in untreated patients (HR=0.70, P=0.29). When HEY1, HES1 and SOX9 expression were combined to predict survival with chemotherapy, in treated patients there was an additive increase in the risk of death with each NTF overexpressed (HR=2.09, P=0.01), but no prognostic import in the untreated patient group (HR=0.74, P=0.19). Conclusion: The present study is the first to discover that HEY1 overexpression correlates with poorer outcome in CRC, and NTF expression is predictive of CRC patient survival with 5-FU chemotherapy. If confirmed in future studies, testing of NTF expression has the potential to enter routine pathological practice for the selection of patients to undergo chemotherapy alone or in combination with Notch inhibitors.

    Related items

    Showing items related by title, author, creator and subject.

    • Molecular mechanism underlying aberrant expression of the connective tissue growth factor in paediatric pre-B cell acute lymphoblastic leukemia
      Welch, Mathew D. (2011)
      Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children aged 1-14 years. There have been vast improvements in clinical outcomes for children diagnosed with ALL with cure rates of up to 90% ...
    • Immunomodulation by MYB is associated with tumor relapse in patients with early stage colorectal cancer
      Millen, R.; Malaterre, J.; Cross, R.; Carpinteri, S.; Desai, J.; Tran, B.; Darcy, P.; Gibbs, P.; Sieber, O.; Zeps, Nikolajs; Waring, P.; Fox, S.; Pereira, L.; Ramsay, R. (2016)
      The presence of tumor immune infiltrating cells (TILs), particularly CD8+ T-cells, is a robust predictor of outcome in patients with colorectal cancer (CRC). We revisited TIL abundance specifically in patients with ...
    • Overexpression of Bcl-2 induces STAT-3 activation via an increase in mitochondrial superoxide.
      Kang, J.; Chong, S.; Ooi, V.; Vali, S.; Kumar, A.; Kapoor, S.; Abbasi, T.; Hirpara, J.; Loh, T.; Goh, B.; Pervaiz, Shazib (2015)
      We recently reported a novel interaction between Bcl-2 and Rac1 and linked that to the ability of Bcl-2 to induce a pro-oxidant state in cancer cells. To gain further insight into the functional relevance of this interaction, ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.