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Jpn J Clin Oncol. 2013 Dec;43(12):1261-8. doi: 10.1093/jjco/hyt160. Epub 2013 Nov 1.

Lower mRNA and protein expression levels of LC3 and Beclin1, markers of autophagy, were correlated with progression of renal clear cell carcinoma.

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1
*No. 157 Xiwu Road, Xi'an, Shaanxi 710004, China. ziming-w@263.net.

Abstract

OBJECTIVE:

The aim of this study was to examine the level of autophagy in renal clear cell carcinoma, stratify by clinicopathologic grades and stages and compare it with healthy renal tissue in order to hypothesize on the role of autophagy in the proliferation of renal clear cell carcinoma.

METHODS:

Renal clear cell carcinoma tissue and matched adjacent tissue were collected from 52 patients who had received surgical resection. Autophagosomes were visualized in both renal clear cell carcinomas and adjacent tissue by transmission electron microscopy. Expression of the markers of autophagy, Beclin1 and LC3, was detected by a reverse transcription-polymerase chain reaction. Beclin1 and LC3 protein levels were examined by immunohistochemistry and western blot, and the correlation between autophagy levels and clinicopathologic data was analyzed.

RESULTS:

Autophagy was down-regulated in renal clear cell carcinomas compared with matched adjacent tissue as measured by the reverse transcriptase-polymerase chain reaction, immunohistochemistry and western blot analyses. Clinicopathologic analyses indicated that advanced or metastatic renal clear cell carcinomas were associated with a lower expression of autophagy compared with localized renal clear cell carcinomas. Similarly, the Fuhrman nuclear grade of renal clear cell carcinomas was negatively correlated with the level of autophagy. Stage, grade and the level of LC3 II were significant factors for prognosis and the low level of LC3 II was associated with poor prognosis of renal clear cell carcinomas.

CONCLUSIONS:

The results indicate that autophagy is suppressed in renal clear cell carcinomas. The lower levels of autophagy are correlated with the higher stages and grades of renal clear cell carcinomas. Furthermore, a low level of LC3 II indicates poor prognosis of renal clear cell carcinoma. This is suggestive of association between the low level of autophagy and progression of renal clear cell carcinoma.

KEYWORDS:

Beclin1; LC3; autophagy; cell death; renal clear cell carcinoma

PMID:
24186908
DOI:
10.1093/jjco/hyt160
[Indexed for MEDLINE]
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