Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma
Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma
复制标题
DOI：
10.1016/j.humpath.2015.07.016
复制
发表时间：
2015-11-01
期刊：
影响因子：
3.3
通讯作者：
Tian Dong
中科院分区：
文献类型：
--
作者：
Wu Shuhua;Sun Chenbo;Tian Dong
本研究旨在评估结直肠癌（CRC）患者中自噬相关基因Raptor、Rictor和Beclin1的表达与多药耐药（MDR）基因表达之间的关系。采用免疫组化和实时聚合酶链反应检测279例结直肠癌标本中哺乳动物雷帕霉素靶蛋白（mTOR）、Raptor、Rictor、Beclin1、轻链3（LC3）和MDR-1的蛋白和信使RNA表达。每年通过电话或在门诊对患者进行随访。结果显示结直肠癌中 Beclin1、LC3、mTOR、Raptor、Rictor 和 MDR-1 的蛋白和信使 RNA 表达量显着高于癌旁组织。低分化CRC中LC3的表达高于高分化CRC，且淋巴结转移中mTOR、Raptor、Rictor和LC3的表达高于无淋巴结转移时的表达。结直肠癌中LC3的表达与Beclin1、Rictor的表达呈正相关，与Raptor、mTOR的表达呈负相关。 Raptor的表达与Rictor呈负相关。 MDR-1的表达与Beclin1、LC3、Rictor的表达呈正相关，与Raptor、mTOR的表达呈负相关。 Kaplan-Meier分析显示无淋巴结转移患者5年生存率； Rictor、Beclin1 和 LC3 阳性表达； Raptor和mTOR的阴性表达高于具有这些特征的人。综上所述，Beclin1、Raptor、Rictor的表达与结直肠癌及MDR的发生、发展有关。 (C) 2015 Elsevier Inc. 保留所有权利。
This study aims to evaluate the relationship between the expressions of autophagy-related genes Raptor, Rictor, and Beclin1 and the expression of multidrug resistance (MDR) gene in colorectal cancer (CRC) patients. Immunohistochemistry and real-time polymerase chain reaction were used to detect the protein and messenger RNA expressions of mammalian target of rapamycin (mTOR), Raptor, Rictor, Beclin1, light chain 3 (LC3), and MDR-1 in 279 CRC specimens. Patients were followed up annually by telephone or at an outpatient clinic. Results revealed that the protein and messenger RNA expressions of Beclin1, LC3, mTOR, Raptor, Rictor, and MDR-1 in CRC are significantly higher than in adjacent tissues. LC3 expression in poorly differentiated CRC is higher than that in well-differentiated CRC, and the expression of mTOR, Raptor, Rictor, and LC3 in lymph node metastasis is higher than that obtained in the absence of lymph node metastasis. The expression of LC3 is positively correlated with those of Beclin1 and Rictor and negatively correlated with Raptor and mTOR in CRC. The expression of Raptor is negatively correlated with Rictor. The expression of MDR-1 is positively correlated with those of Beclin1, LC3, and Rictor and negatively correlated with Raptor and mTOR. Kaplan-Meier analysis revealed that the 5-year survival rate of patients without lymph node metastasis; positive expression of Rictor, Beclin1, and LC3; and negative expression of Raptor and mTOR were higher than those with these characteristics. To conclude, the expressions of Beclin1, Raptor, and Rictor are related to the development and progression of colorectal carcinoma and MDR. (C) 2015 Elsevier Inc. All rights reserved.