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ID 36285
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title alternative
nardilysinをコードするNRD1は、MMP2およびMMP3を介して食道がんの浸潤を促進させる
creator
Uraoka, Naohiro
subject
Esophageal cancer
NRD1
nardilysin
prognosis
invasion
NDC
Medical sciences
abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. In the present study, to identify novel prognostic markers or therapeutic targets for ESCC, we reviewed a list of genes with upregulated expression in ESCC compared with normal esophagus, as identified by our serial analysis of gene expression (SAGE) analysis. We focused on the NRD1 gene, which encodes the nardilysin protein. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in 34 ESCC tissue samples revealed that mRNA expression of NRD1 was upregulated in 56% of ESCC tissue samples. Immunohistochemical analysis of nardilysin in 109 ESCC tissue samples demonstrated that 43 (39%) ESCC cases were positive for nardilysin. Nardilysin-positive ESCC cases were more advanced in terms of T classification (P = 0.0007), N classification (P = 0.0164), and tumor stage (P < 0.0001) than nardilysin-negative ESCC cases. Furthermore, nardilysin expression was significantly associated with poorer prognosis (P = 0.0258). Univariate and multivariate analyses revealed that nardilysin expression is an independent prognostic classifier of patients with ESCC. The invasiveness of NRD1-knockdown TE1 and TE5 esophageal cancer cell lines was less than that of the negative control siRNA-transfected cell lines. Expression of MMP2 and MMP3 mRNA was significantly lower in NRD1-knockdown TE5 cells than in negative control siRNA-transfected cells. These results suggest that nardilysin is involved in tumor progression, and is an independent prognostic classifier in patients with ESCC.
date of created
2014-11-21
language
eng
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
text version
ETD
rights
Copyright(c) by Author
relation references
Naohiro Uraoka, Naohide Oue, Naoya Sakamoto, Kazuhiro Sentani, Htoo Zarni Oo, Yutaka Naito, Tsuyoshi Noguchi and Wataru Yasui; NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression; Cancer Science, Volume 105, Issue 1, pages 134-140, January 2014 (DOI: 10.1111/cas.12316)
relation references URL
http://dx.doi.org/10.1111/cas.12316
grantid
甲第6284号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(医学)
degreename En
Philosophy in Medical Science
degreelevel
doctoral
date of granted
2014-02-27
department
Graduate School of Biomedical Science