Lower mRNA and Protein Expression Levels of LC3 and Beclin1, Markers of Autophagy, were Correlated with Progression of Renal Clear Cell Carcinoma
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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DOI：
10.1093/jjco/hyt160
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发表时间：
2013-12-01
影响因子：
2.4
通讯作者：
Chong, Tie
中科院分区：
文献类型：
--
作者：
Deng, Qian;Wang, Zhenlong;Chong, Tie
本研究的目的是检测肾透明细胞癌中自噬的水平，根据临床病理分级和分期进行分层，并与正常肾组织进行比较，以推测自噬在肾透明细胞癌增殖中的作用。在透射电子显微镜下，肾透明细胞癌及癌旁组织中均可见自噬小体。逆转录-聚合酶链式反应检测自噬标志物Beclin1和Lc3的表达。免疫组织化学和免疫印迹法检测Beclin1和Lc3蛋白水平，并分析自噬水平与临床病理资料的相关性。逆转录聚合酶链式反应、免疫组织化学和Western印迹分析表明，肾透明细胞癌组织中自噬水平较癌旁组织下调。临床病理分析表明，与局限性肾透明细胞癌相比，晚期或转移性肾透明细胞癌的自噬表达较低。同样，肾透明细胞癌的Fuhrman核分级与自噬水平呈负相关。肾透明细胞癌的分期、分级和水平是影响预后的重要因素，低水平的LC_3 II与预后不良有关，提示肾透明细胞癌自噬功能受到抑制。自噬水平越低，肾透明细胞癌的分期和分级越高。此外，低水平的LC_3 II提示肾透明细胞癌预后不良。这提示低水平的自噬与肾透明细胞癌的进展有关。
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.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 transcriptionpolymerase 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.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.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.