自噬相关蛋白在肾透明细胞癌与癌旁组织中表达状况的比较研究

Comparison of autophagy related proteins expression between clear cell renal cell carcinoma and adjacent tissue

目的 检测自噬表达水平在正常组织和肾透明细胞癌组织中的差异. 方法 2011年1-4月采用免疫组化方法检测69例肾透明细胞癌患者的正常组织和肿瘤组织中自噬相关蛋白（p-mTOR、P62、LC3、Beclin 1、ULK1、ATG5、ATG7）表达的差异,并对其表达差异及各蛋白间表达量变化的相关性进行统计学分析.2011年8月采用透射电镜对4例肾癌患者的正常组织和肿瘤组织进行细胞超微结构的分析. 结果 与正常组织相比,p-mTOR（P=0.004）、P62（P=0.000）和ULK1（P=0.000）在肿瘤组织中的表达上调,而Beclin 1（P=0.000）、LC3（P=0.000）和ATG7（P=0.000）的表达下调,差异均有统计学意义.ATG5表达量无明显变化（P=0.349）.形态分析结果显示肿瘤细胞内的自噬体数量少于正常组织.p-mTOR与P62（P=0.026）、LC3（P=0.027）和ATG7（P=0.049）的表达水平变化之间具有相关性,而与Beclin 1不相关. 结论 自噬的表达水平在肾透明细胞癌中下调,其下调受mTOR等多种自噬相关蛋白的协同影响.

Objective To investigate the autophagy capacity in clear cell renal cell carcinoma tissue compared with adjacent normal tissue. Methods Sixty-nine pairs of samples from human clear cell renal cell carcinoma tissues and relatively healthy renal tissues adjacent to the tumor were collected during surgical resection. The expressions of proteins that were participating in the regulation and execution of autophagy were detected by immunohistochemisty. Electron-microscopy was also carried out for the morphometrical analysis. Results The protein expression of p-mTOR （P=O.004） , P62 （P=0.000） and ULK1 （P= 0.000） were up-regulated in the carcinoma tissue, while the expression of Beclinl （P= 0.000） , LC3 （P= 0.000） and ATG7 （P = 0.000） were down-regulated, and the expression of ATG5 （P = 0.349） had no signif- icant difference compared with adjacent normal tissue. Morphometrical analysis showed that the basal autoph- agic activity （measured by the presence of autophagy vacuole compartment） was remarkably down-regulated in carcinoma tissue, compared with adjacent normal tissue. The expression level of mTOR was correlated with P62, LC3 and ATGT, but results showed no correlation between mTOR and Beclin 1. Conclusion Our studies show a relatively reduced autophagy capacity in clear cell renal cell carcinoma, which is regula- ted by multiple autophagy-related proteins such as mTOR, Beclin 1 and LC3.