PMID- 31535245
OWN - NLM
STAT- MEDLINE
DCOM- 20200611
LR  - 20200611
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Linking)
VI  - 25
IP  - 3
DP  - 2020 Mar
TI  - Overexpression of Cullin4A correlates with a poor prognosis and tumor progression 
      in esophageal squamous cell carcinoma.
PG  - 446-455
LID - 10.1007/s10147-019-01547-2 [doi]
AB  - 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.
FAU - Nakade, Hiroshi
AU  - Nakade H
AUID- ORCID: 0000-0001-9798-7355
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan. nakad@naramed-u.ac.jp.
FAU - Migita, Kazuhiro
AU  - Migita K
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
FAU - Matsumoto, Sohei
AU  - Matsumoto S
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
FAU - Wakatsuki, Kohei
AU  - Wakatsuki K
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
FAU - Kunishige, Tomohiro
AU  - Kunishige T
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
FAU - Miyao, Shintaro
AU  - Miyao S
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
FAU - Sho, Masayuki
AU  - Sho M
AD  - Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 
      634-8521, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190918
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Cell Proliferation/genetics
MH  - Cullin Proteins/*genetics/metabolism
MH  - Esophageal Neoplasms/*genetics/*mortality/pathology/surgery
MH  - Esophageal Squamous Cell Carcinoma/*genetics/*mortality/pathology/surgery
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Prognosis
MH  - RNA, Small Interfering
OTO - NOTNLM
OT  - Cullin4A
OT  - E3 ubiquitin ligase
OT  - Esophageal squamous cell carcinoma
OT  - Recurrence
OT  - p21 protein
EDAT- 2019/09/20 06:00
MHDA- 2020/06/12 06:00
CRDT- 2019/09/20 06:00
PHST- 2019/05/06 00:00 [received]
PHST- 2019/09/10 00:00 [accepted]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/06/12 06:00 [medline]
PHST- 2019/09/20 06:00 [entrez]
AID - 10.1007/s10147-019-01547-2 [pii]
AID - 10.1007/s10147-019-01547-2 [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2020 Mar;25(3):446-455. doi: 10.1007/s10147-019-01547-2. Epub 
      2019 Sep 18.