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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3739

Title: Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma.
Other Titles: 食道扁平上皮癌における予後因子および腫瘍進展メカニズムとCullin4A高発現との関連性について
Authors: Nakade, Hiroshi
Migita, Kazuhiro
Matsumoto, Sohei
Wakatsuki, Kohei
Kunishige, Tomohiro
Miyao, Shintaro
Sho, Masayuki
Keywords: Cullin4A
Esophageal squamous cell carcinoma
E3 ubiquitin ligase
p21 protein
Recurrence
Issue Date: Mar-2020
Publisher: Springer Nature
Citation: International journal of clinical oncology Vol.25 No.3 p.446-455 (2020 Mar)
Abstract: Background: Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown. Methods: We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique. Results: The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels. Conclusions: CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.
Description: 博士(医学)・乙第1449号・令和2年3月16日
© Japan Society of Clinical Oncology 2019
This is a post-peer-review, pre-copyedit version of an article published in International journal of clinical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10147-019-01547-2.
発行元が定める登録猶予期間終了の後、本文を登録予定(2021.03)
URI: http://hdl.handle.net/10564/3739
ISSN: 13419625
Academic Degrees and number: 24601B1449
Degree-granting date: 2020-03-16
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2019年度

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