Clear cell renal cell carcinoma （ccRCC） is one frequent form of urologic malignancy with numerous genetic and epigenetic alterations. This review summarizes the recent major findings of epigenetic alterations includ...Clear cell renal cell carcinoma （ccRCC） is one frequent form of urologic malignancy with numerous genetic and epigenetic alterations. This review summarizes the recent major findings of epigenetic alterations including DNA methylation, histone modifications, microRNAs and recently identified long noncoding RNAs in the development and progression of ccRCC. These epigenetic profilings can provide a promising means of prognostication and early diagnosis for patients with ccRCCs. With the developed high- throughput technologies nowadays, the epigenetic analyses will have possible clinical applications in the molecular pathology of ccRCC.展开更多
Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the dif...Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the differences in the expression of DNMT1 in 89 ecRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines （786-0 and Caki-1） were assessed after transfection with DNMT1 siRNA. Results： We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues （56.2% and 27.3%, respectively, P=0.018）. The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions： Expression of DNMTI protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.展开更多
Objective:The aim of the study was to investigate the clinicopathologic significance of caveolin-1 expression in clear cell renal cell carcinoma (CCRCC) and its correlation with microvessel density (MVD).Methods:The e...Objective:The aim of the study was to investigate the clinicopathologic significance of caveolin-1 expression in clear cell renal cell carcinoma (CCRCC) and its correlation with microvessel density (MVD).Methods:The expression of caveolin-1 was detected by the immunohistochemistry method,while the microvessel density was detected by the immunohistochemistry expression of CD34.Results:In the CCRCCs,the positive rate of caveolin-1 was 67.4%,the over expression of caveolin-1 was not related with sex and age,but related with clinicopathologic parameter,such as tumor sizes,clinical TMN stage,nuclear stage and survival time (P < 0.05).The MVD of positive caveolin-1 cases was significantly higher than that without caveolin-1 expression (P < 0.05).Conclusion:The expression of caveolin-1 is helpful in the prognostic evaluation of CCRCCs and it may be involved in the tumor angiogenesis.展开更多
目的:构建基于上皮间质相互作用蛋白1(epithelial-stromal interaction protein 1,EPSTI1)预后列线图预测肾透明细胞癌的预后。方法:回顾性分析2012年1月至2015年12月于福建医科大学附属第一医院221例接受手术治疗的肾透明细胞癌患者和T...目的:构建基于上皮间质相互作用蛋白1(epithelial-stromal interaction protein 1,EPSTI1)预后列线图预测肾透明细胞癌的预后。方法:回顾性分析2012年1月至2015年12月于福建医科大学附属第一医院221例接受手术治疗的肾透明细胞癌患者和TCGA数据库中533例肾透明细胞癌患者数据,对癌旁正常组织和癌组织标本进行免疫组织化学(immunohistochemistry,IHC)染色,分析EPSTI1的表达差异及与临床病理特征的相关性。对EPSTI1高表达与低表达患者的总生存期(overall survival,OS)和无病生存期(disease-free survival,DFS)进行Kaplan-Meier生存分析,采用单因素和多因素Cox比例风险模型分析OS的预后因素,进一步构建列线图模型并验证。结果:与癌旁正常肾组织比较,肾透明细胞癌组织中EPSTI1的IHC评分和m RNA表达水平均显著高于正常组织(均P<0.001),且在高T分期的癌组织中表达更高(P=0.036,P=0.006);EPSTI1蛋白表达与肿瘤最大径、TNM分期相关(P=0.002,P=0.032);EPSTI1低表达组OS、DFS均优于高表达组(P=0.046,P=0.003,P=0.001);单因素和多因素Cox回归分析结果显示,EPSTI1蛋白高表达、WHO/ISUP分级、AJCC/TNM分期是影响肾透明细胞癌患者预后不良的独立危险因素(P=0.009,P=0.039,P<0.001);基于上述变量构建的预后列线图模型对患者5年OS预测能力优于AJCC/TNM分期,校准曲线显示模型预测值与实际值间具有良好的一致性。结论:基于EPSTI1、AJCC/TNM分期和WHO/ISUP分级建立的列线图模型对肾透明细胞癌预后具有较强的预测能力。展开更多
目的探讨线粒体DNA D-loop(mt DNA D-loop)基因多态性与肾透明细胞癌患者(CCRCC)发病年龄的关系。方法采用聚合酶链反应(PCR)对59例CCRCC患者的mt DNA D-loop区进行扩增并测序。将mt DNA D-loop区的测序结果与线粒体文库中的剑桥序列(r ...目的探讨线粒体DNA D-loop(mt DNA D-loop)基因多态性与肾透明细胞癌患者(CCRCC)发病年龄的关系。方法采用聚合酶链反应(PCR)对59例CCRCC患者的mt DNA D-loop区进行扩增并测序。将mt DNA D-loop区的测序结果与线粒体文库中的剑桥序列(r CRS)比对进行单核苷酸多态性(SNP)分析。单核苷酸多态性与患者发病年龄关系的分析采用Kaplan-Meier方法,组间比较采用Log-rank检验,多因素分析采用Cox比例风险回归模型。结果单因素分析显示,高TNM分期组患者的发病年龄低于低TNM分期组;肿瘤直径≥5 cm的患者发病年龄低于肿瘤直径<5 cm的患者(均P<0.05),单核苷酸多态位点16293A/G基因型与发病年龄有关,多态位点16293G基因型患者的发病年龄明显早于16293A基因型患者(P<0.05)。多因素分析显示,TNM分期高低、肿瘤直径大小、16293位点的多态性是影响肾透明细胞癌患者发病年龄的独立危险因素。结论线粒体DNA D-loop区基因多态性可作为肾透明细胞癌患者发病年龄的预测因素,同时线粒体DNA D-loop区基因多态性有助于识别早发的肾透明细胞癌。展开更多
文摘Clear cell renal cell carcinoma （ccRCC） is one frequent form of urologic malignancy with numerous genetic and epigenetic alterations. This review summarizes the recent major findings of epigenetic alterations including DNA methylation, histone modifications, microRNAs and recently identified long noncoding RNAs in the development and progression of ccRCC. These epigenetic profilings can provide a promising means of prognostication and early diagnosis for patients with ccRCCs. With the developed high- throughput technologies nowadays, the epigenetic analyses will have possible clinical applications in the molecular pathology of ccRCC.
基金supported by grants from National Natural Science Foundation of China (No. 30873097)
文摘Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the differences in the expression of DNMT1 in 89 ecRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines （786-0 and Caki-1） were assessed after transfection with DNMT1 siRNA. Results： We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues （56.2% and 27.3%, respectively, P=0.018）. The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions： Expression of DNMTI protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.
基金Supported by a grant from the Technology Development Foundation of the Pudong New District(No. PKJ2009-Y24)
文摘Objective:The aim of the study was to investigate the clinicopathologic significance of caveolin-1 expression in clear cell renal cell carcinoma (CCRCC) and its correlation with microvessel density (MVD).Methods:The expression of caveolin-1 was detected by the immunohistochemistry method,while the microvessel density was detected by the immunohistochemistry expression of CD34.Results:In the CCRCCs,the positive rate of caveolin-1 was 67.4%,the over expression of caveolin-1 was not related with sex and age,but related with clinicopathologic parameter,such as tumor sizes,clinical TMN stage,nuclear stage and survival time (P < 0.05).The MVD of positive caveolin-1 cases was significantly higher than that without caveolin-1 expression (P < 0.05).Conclusion:The expression of caveolin-1 is helpful in the prognostic evaluation of CCRCCs and it may be involved in the tumor angiogenesis.
文摘术前预测透明细胞肾细胞癌(clear cell renal cell carcinoma,ccRCC)的分级可有效评估患者的预后并指导临床治疗,但实现精准预测是目前本领域内的一项重要问题。该研究首先确定最优建模的CT类型与网络层数,提出了一种基于改进残差网络的ccRCC的CT影像分级模型,具体包括:利用大卷积操作对图像进行原始特征提取,利用混合注意力模块通过计算特征图中当前空间和临近空间以及当前空间和远距离空间之间的信息交互获取更多有用的特征,使得原始图像特征图在通道维度与空间维度上进行自适应特征细化,利用四个深度卷积网络层提取图像深度特征,并利用改进通道注意力模块产生通道注意力特征图信息,提取更多通道上的交互信息。实验结果表明,增强CT实质期图像和34层残差网络最有利于分级预测模型的开发,所提出的模型的总体加权准确率、AUC、精度、召回率和F1分数分别为90.8%、0.897、90.5%、90.8%、90.9%,各项指标优于其他常见网络结构,因此,该模型在预测ccRCC的国际泌尿病理学学会(International Society of Urological Pathology,ISUP)分级方面有良好的效能,对患者的临床辅助诊断和预后治疗具有重要的理论指导意义。
文摘目的探讨线粒体DNA D-loop(mt DNA D-loop)基因多态性与肾透明细胞癌患者(CCRCC)发病年龄的关系。方法采用聚合酶链反应(PCR)对59例CCRCC患者的mt DNA D-loop区进行扩增并测序。将mt DNA D-loop区的测序结果与线粒体文库中的剑桥序列(r CRS)比对进行单核苷酸多态性(SNP)分析。单核苷酸多态性与患者发病年龄关系的分析采用Kaplan-Meier方法,组间比较采用Log-rank检验,多因素分析采用Cox比例风险回归模型。结果单因素分析显示,高TNM分期组患者的发病年龄低于低TNM分期组;肿瘤直径≥5 cm的患者发病年龄低于肿瘤直径<5 cm的患者(均P<0.05),单核苷酸多态位点16293A/G基因型与发病年龄有关,多态位点16293G基因型患者的发病年龄明显早于16293A基因型患者(P<0.05)。多因素分析显示,TNM分期高低、肿瘤直径大小、16293位点的多态性是影响肾透明细胞癌患者发病年龄的独立危险因素。结论线粒体DNA D-loop区基因多态性可作为肾透明细胞癌患者发病年龄的预测因素,同时线粒体DNA D-loop区基因多态性有助于识别早发的肾透明细胞癌。
