CD248在肾透明细胞癌中的表达及临床意义CSCD

目的探讨内皮唾酸蛋白(CD248)在肾透明细胞癌(ccRCC)组织中的表达及临床意义。方法收集115例ccRCC组织及对应癌旁组织的石蜡标本,同时收集其中17例ccRCC组织及对应癌旁组织的新鲜标本。qRT-PCR检测17例ccRCC组织及对应癌旁组织中CD248 mRNA的表达;免疫组织化学法检测115例ccRCC患者石蜡标本的CD248蛋白水平,分析CD248表达与ccRCC临床病理指标及预后的相关性。结果ccRCC组织中的CD248阳性表达免疫组织化学反应强度显著强于癌旁组织,差异有统计学意义(P=0.0061),且CD248蛋白阳性信号定位于细胞核及细胞质。CD248 mRNA在癌旁组织中的表达水平明显低于ccRCC组织(P=0.0026)。CD248高表达组组间总生存率明显低于CD248低表达组(44.4 vs.57.2月,P=0.017)。结论CD248的表达可能参与ccRCC的发生发展。与癌旁组织比较,CD248在ccRCC组织中高表达;CD248高表达的ccRCC患者术后生存时间较短。     

TGF-β-activated Kinase-1: A Potential Prognostic Marker for Clear Cell Renal Cell Carcinoma

Background: TGF-β-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solidmalignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. TissueTAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluationof relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantlyhigher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression ofTAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples wassignificantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not ageand gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage wereindependent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.     

Low Expression of ATM Indicates a Poor Prognosis in Clear Cell Renal Cell Carcinoma

IntroductionThe study was carried out to examine the expression of ataxia telangiectasia mutant (ATM) of clear cell renal cell carcinoma (ccRCC), and to explore the relationship between the expression of ATM and the clinicopathologic parameters and prognosis of ccRCC.Materials and MethodsClinicopathologic data of the patients with ccRCC were collected from January 2011 to August 2015 in Xiangya Hospital, Central South University. The immunohistochemical method was used to detect the expression of ATM in ccRCC and adjacent tissues. The Kaplan-Meier survival method and log-rank test were used to analyze the relationship between ATM expression and the survival time of the patients with ccRCC. Univariate and multivariate Cox regression analysis was used to evaluate the risk factors for the prognosis of ccRCC.ResultsA total of 110 patients were selected in this study, including 73 men and 37 women. The expression of ATM in ccRCC is significantly lower than that in adjacent tissues. Further analysis found that the expression of ATM in the ccRCC tissues above grade II was lower than that of grade II or below. Kaplan-Meier survival analysis showed that the total survival time of the ATM low expression group was significantly shorter than that of the ATM high expression group. The multivariate Cox regression analysis showed that expression of ATM and clinical stage were independent factors affecting the prognosis of ccRCC.ConclusionATM expression level could serve as an independent risk factor for the prognosis of ccRCC and could be considered as a potential therapeutic target of ccRCC.     

Differential Expression of IQGAP1/2 in Hepatocellular Carcinoma and its Relationship with Clinical Outcomes

Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (Ⅲ and Ⅳ, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (Ⅲ and Ⅳ, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.     

触珠蛋白HP在肾透明细胞癌中的表达及临床意义

目的:研究触珠蛋白HP在肾透明细胞癌中的表达及临床意义,为肾透明细胞癌的医治提供新的生物治疗靶点和理论依据。方法:从美国癌症基因组图谱(TCGA)中下载肾透明细胞癌的相关基因数据,进行筛选后获得目的基因HP。利用免疫组化研究该基因在肾透明细胞癌组织及癌旁组织中的差异化表达,以及与临床数据的相关性,随后利用R软件对TCGA数据库中的病例样本进一步分析予以验证,并分析HP与临床预后的关系。结果:TCGA数据库中总共得到611个样本(其中癌旁组织样本72个,癌组织样本539个),挑选后得到1 925个差异基因。筛选后选择HP为目标基因,免疫组化表明HP在肾透明细胞癌组织中阳性率（66.0%）高于癌旁组织（36.0%）(P=0.005),并且该基因的表达与WHO/ISUP核分级差异有统计学意义（P<0.05）,与性别、年龄及T分期差异无统计学意义（P> 0.05）。对TCGA数据库样本分析发现HP的表达水平与T分期、N分期、性别及TNM分期的差异有统计学意义（P<0.05）,而与年龄、M分期的差异无统计学意义（P> 0.05）,并且HP高表达组的预后较低表达组更差。结论...     

Overexpression of Cyclooxygenase-1 Correlates with Poor Prognosis in Renal Cell Carcinoma

The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognosticvalue. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative realtimepolymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 inRCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemicalassays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated highexpression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p= 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients withhigh expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. Thisis the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affectedpatients.     

RNA结合蛋白QKI-5在肾透明细胞癌中的表达及临床意义

目的:比较QKI-5在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）及癌旁组织中的表达水平,并分析其表达水平与临床病理特征及预后之间的关系。方法:收集68例经手术切除的肾透明细胞癌及相应的癌旁组织标本,提取标本的总RNA,经反转录获得cDNA,并通过实时荧光定量PCR(qRT-PCR)方法检测QKI-5的表达水平,利用统计学方法分析其表达量与患者临床病理特征及预后之间的关系。结果:68例组织标本中有49例（72.06%）癌组织的QKI-5表达水平降低,统计学分析表明QKI-5表达水平的降低和肿瘤的T分期及病理G分级升高相关。Kaplan-Meier生存分析显示,QKI-5高表达的肾癌患者总生存期优于低表达者（P=0.009）。Cox多因素分析显示QKI-5表达水平降低是影响患者预后的独立不良因子。结论:QKI-5在肾透明细胞癌组织中低表达,QKI-5低表达和肿瘤的T分期及病理G分级升高相关,与肾透明细胞癌不良预后有关。     

TNFAIP3在透明细胞肾细胞癌中的表达及临床意义

目的:探讨TNFAIP3在透明细胞肾细胞癌（clear cell renal cell carcinoma,ccRCC）中的表达情况,并分析其表达与患者临床病理特征的相关性。方法:利用GEPIA2数据库分析TNFAIP3在ccRCC组织和正常肾脏组织中的差异表达,收集具备完整临床资料的97例ccRCC组织及对应的癌旁正常肾脏组织,采用免疫组织化学EnVision两步法检测TNFAIP3蛋白在ccRCC组织及对应癌旁正常肾脏组织中的表达,分析TNFAIP3蛋白的表达情况与患者年龄、性别、WHO/ISUP分级、肿瘤最大径及TNM分期等临床病理特征的关系。结果:GEPIA2数据库分析显示,与正常肾脏组织相比TNFAIP3在ccRCC组织中呈高表达（P＜0.05）,但TNFAIP3高表达ccRCC患者总生存时间和无瘤生存时间均显著高于TNFAIP3低表达ccRCC患者（P＜0.05）;TNFAIP3免疫组化检测证实,TNFAIP3在ccRCC组织中呈淡黄至棕褐色表达于细胞膜和细胞质,在ccRCC组织中高表达比例明显高于癌旁正常肾脏组织（P＜0.05）,TNFAIP3表达水平与ccRCC组织的WHO/ISUP肾细胞癌分级、肿瘤最大径、TNM分期、有无淋巴结转移临床参数有关（P＜0.05）,TNFAIP3高表达则提示较好的预后。结论:ccRCC组织中TNFAIP3的表达明显升高,而TNFAIP3高表达的ccRCC患者总生存期和无瘤生存期均好于TNFAIP3低表达的ccRCC患者,TNFAIP3参与ccRCC增殖、转移中的作用方式与分子调控机制则待进一步研究。     

Nucleostemin mRNA is expressed in both normal and malignant renal tissues

Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.     

趋化因子CCL5表达与肾透明细胞癌病理特征及预后的相关性研究

目的:明确趋化因子CCL5表达水平与肾透明细胞癌患者病理特征及患者预后的相关性。方法:收集本院2006年1月至2014年1月行手术治疗并术后病理证实为肾透明细胞癌患者肿瘤及对应癌旁组织标本（90例）,术后随访时间为18~90个月,应用免疫组织化学、蛋白印迹法、ELISA方法分别检测趋化因子CCL5表达、血清浓度状况,分析CCL5表达与肾脏透明细胞癌临床病理特征及预后的关系。结果:肾透明细胞癌患者血清中趋化因子CCL5浓度显著高于正常非肿瘤患者（P=0.015 2）;趋化因子CCL5在肾透明细胞癌组织内蛋白表达水平显著高于癌旁组织（P<0.01）;CCL5表达强度与肿瘤大小（P<0.01）、病理分级（P<0.01）、临床分期（P<0.05）呈正相关性,而与性别与年龄关系不密切（P>0.05）;CCL5表达强度与患者总生存时间（OR）呈负相关性且具有显著性差异（P<0.001）。结论:趋化因子CCL5表达水平与透明细胞癌患者病理特征及预后关系密切,其异常高表达可能是促进透明细胞癌发生发展的重要原因,并有可能作为肾透明细胞癌早期监测指标及潜在治疗靶点。     

ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

Hyperactivated α2-6-sialylation on N-glycans due to overexpression of the Golgi enzyme β-galactoside: α2-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This studywas aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival ofpatients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at asingle center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinicaloutcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016,respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 andp=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overallsurvival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002,respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expressionremained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggestedthat the association is more pronounced among patients with low and intermediate-risk disease defined by theUISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrencein ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk diseasedefined by the UISS score.     

基于TCGA数据库分析CRB3在肾透明细胞癌（ccRCC）中的表达及其与预后的关系

目的:通过研究细胞极性蛋白CRB3（Crumbs 3）在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）组织中的表达,阐明其对ccRCC早期诊断及预后的作用。方法:运用癌症基因组图谱（TCGA）数据库和免疫组织化学（immunohistochemistry,IHC）技术分析CRB3在ccRCC组织和正常肾组织的表达情况,通过LinkedOmics和GEPIA阐述CRB3表达与ccRCC临床病理学参数的相关性及对预后的影响。结果:CRB3 mRNA在ccRCC中低表达,并且与ccRCC病理分级、TNM分期呈负相关,并与人种相关。TCGA结果显示CRB3低表达是影响ccRCC患者总生存率和无病生存率的独立预后因素（P<0.05）。IHC结果证实,与正常肾组织相比,ccRCC中CRB3的蛋白表达量显著降低（P<0.05）。结论:在ccRCC中,CRB3低表达是一种重要的不良预后指标,可以作为预测患者转移发生、判断预后的有效生物标志物。     

Survivin and HLA-I expression predicts survival of patients with clear cell renal cell carcinoma

Altered expression of survivin and leukocyte antigen class I (HLA-I) proteins is associated with tumor progression. This study investigated their expressions in clear cell renal cell carcinoma (ccRCC) tissues for association with a clinical significance of ccRCC patients. Ninety ccRCC and 20 normal tissue samples (i.e., control) were immunohistochemically stained for survivin and HLA-I expression for an association with clinicopathological data and survival of ccRCC patients. Survivin protein was expressed in 82.2 % (74/90) of ccRCC tissue samples compared to 0 % in the normal tissues, and HLA-I protein was expressed in 90 % (18/20) of the normal tissues vs. 67.8 % (61/90) in ccRCC samples. Survivin expression was associated with tumor grade, stage, and lymph node metastasis (p?=?0.000, p?=?0.016, and p?=?0.001, respectively). Conversely, lost HLA-I expression did not have any associations with clinicopathological data (p?>?0.05). Survivin-negative patients had a higher tumor-free survival rate than patients with survivin expression (p?=?0.037). Patients with normal HLA-I levels had a higher tumor-free survival rate than those with reduced HLA-I levels (p?=?0.02). The uni- and multivariate analyses indicated that expression of survivin and HLA-I, individually and in combination, was an independent predictor for survival of ccRCC patients. Overexpression of survivin but reduced HLA-I expression is useful in the prediction of tumor-free survival of ccRCC patients.     

细胞骨架相关蛋白4在肾透明细胞癌中的表达及其临床意义

目的 探讨细胞骨架相关蛋白4(cytoskeleton-associated protein 4,CKAP4)在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的表达及其临床意义。方法 收集237例ccRCC患者的癌组织和癌旁组织,采用免疫组化法检测CKAP4蛋白的表达水平,采用χ²检验比较不同CKAP4蛋白表达水平患者的临床病理特征,Kaplan-Meier法和Log-rank检验分析不同CKAP4表达水平患者总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)的差异,Cox比例风险回归分析影响ccRCC患者术后OS和PFS的因素。结果 ccRCC组织中CKAP4蛋白的高表达率显著高于癌旁组织(54.0%vs 23.6%,χ²=46.050,P<0.001)。Fuhrman分级高、肿瘤浸润深、有淋巴结转移、远处转移以及TNM分期高的ccRCC患者癌组织中CKAP4蛋白高表达(均P<0.05)。CKAP4蛋白高表达...     

Genomics and epigenomics of clear cell renal cell carcinoma: Recent developments and potential applications

Majority of clear cell renal cell carcinomas (ccRCCs) are diagnosed in the advanced metastatic stage resulting in dramatic decrease of patient survival. Thereby, early detection and monitoring of the disease may improve prognosis and treatment results. Recent technological advances enable the identification of genetic events associated with ccRCC and reveal significant molecular heterogeneity of ccRCC tumors. This review summarizes recent findings in ccRCC genomics and epigenomics derived from chromosomal aberrations, DNA sequencing and methylation, mRNA, miRNA expression profiling experiments. We provide a molecular insight into ccRCC pathology and recapitulate possible clinical applications of genomic alterations as predictive and prognostic biomarkers.     

肾透明细胞癌组织中RSK4的表达及临床意义

目的:检测核糖体S6蛋白激酶4（RSK4）在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）中的表达,探讨其高表达与预后及对肾癌细胞系增殖的影响。方法:采用免疫组织化学EnVision法检测48例ccRCC标本及20例肾盂积水标本中RSK4蛋白的表达,用统计学方法分析RSK4的表达与患者临床病理特征及预后的关系;建立过表达RSK4的肾癌细胞系,检测RSK4过表达对肾癌细胞周期及增殖的影响。结果:48例ccRCC肿瘤组织标本中,RSK4的阳性率为75%（36/48）;在20例肾盂积水患者中,RSK4的阳性率为25%（5/20）,二者具有统计学差异（P＜0.05）;经统计学分析,RSK4的表达与ccRCC患者的年龄、性别之间未见明确相关性（P＞0.05）,但与肾透明细胞癌的WHO/ISUP分级显著相关（P=0.019）;单因素及多因素生存分析发现,RSK4的表达及WHO/ISUP分级与患者预后相关（P＜0.05）;过表达RSK4的肾癌细胞系增殖能力显著增强,对细胞周期也有明显的影响（P＜0.05）。结论:RSK4在ccRCC中的表达显著升高,与预后相关;RSK4过表达对肾癌细胞系的周期、增殖均有显著影响,提示RSK4在肾透明细胞癌中高表达,可能通过促进细胞增殖导致预后不良,而其具体作用机制尚有待进一步研究。     

TMEM45A在肾透明细胞癌中的表达及作用机制研究

目的 探讨TMEM45A(Transmembrane protein 45A,TMEM45A)在肾透明细胞癌(Clear cell renal cell carcinoma,ccRCC)中的表达及作用。方法 利用R语言提取Oncomine数据库中TMEM45A相关研究的数据;利用GEPIA数据库在线分析TMEM45A表达水平与肾透明细胞癌分期及生存时间的关系;实时定量PCR和Western blot检测TMEM45A在肾透明细胞癌组织及肾癌细胞系中的表达;应用针对TMEM45A的siRNA转染Caki-1细胞后,实时定量PCR和Western blot验证TMEM45A表达降低,CCK8分析抑制TMEM45A表达后对细胞增殖的影响,实时定量PCR和Western blot分析低表达TMEM45A抑制细胞增殖的作用机制。结果 Oncomine数据库中共收集了384项TMEM45A相关的研究,35项有统计学差异,其中25项表达升高、10项表达降低。有4项研究与ccRCC相关,共有115例样本。分析发现,ccRCC中TMEM45A表达显著升高(P＜0.05);同时发现高表达的TMEM45A与ccRCC高分期及预后不良密切相关(P＜0.05)。与正常的肾脏组织相比,TMEM45A mRNA在肾透明细胞癌组织中表达明显升高(P＜0.05)。人肾癌Caki-1和786-0细胞中TMEM45A mRNA和蛋白表达高于正常肾小管上皮HK-2细胞。TMEM45A siRNA转染Caki-1细胞48 h、72 h后,细胞的增殖能力显著下降(P＜0.001)。同时发现抑制TMEM45A后,PCNA和Cyclin D1蛋白和mRNA表达明显下降(P＜0.05)。结论 TMEM45A在ccRCC中表达升高且与ccRCC分期、预后相关,可能通过调控PCNA和Cyclin D1参与肾癌细胞的增殖。     

免疫相关基因HCST对肾透明细胞癌预后的影响及其机制

目的:分析造血细胞信号转导因子(hematopoietic cell signal transducer,HCST)在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）中的表达及与ccRCC预后、免疫浸润的关系,探讨HCST对ccRCC细胞生长侵袭的影响及其作用机制。方法:利用TCGA数据库分析HCST基因在ccRCC组织中的表达水平。Cox比例风险模型分析HCST表达水平及临床特征与ccRCC患者预后的关系。肿瘤免疫评分数据库（tumor immune estimation resource,TIMER）分析ccRCC组织中HCST表达水平与免疫细胞浸润程度的相关性。体外培养ACHN细胞,分为对照组、siRNA阴性对照组和HCST siRNA组。MTT法、流式细胞实验和Transwell实验分别检测各组ACHN细胞增殖、凋亡和侵袭活性。蛋白质印迹法检测caspase-3、Bax、Bcl-2、E-cadherin、N-cadherin和Vimentin蛋白的表达。结果:与正常肾脏组织比较,HCST mRNA在ccRCC组织中的表达显著上调,且与肿瘤的分期、淋巴转移及远处转移正相关(P＜0.01)。HCST高表达、肿瘤T分期及M分期是影响 ccRCC患者预后的独立危险因素(P＜0.05)。ccRCC中HCST表达与CD8+T细胞、树突状细胞、NK细胞及Treg细胞的浸润程度正相关(P＜0.001)。与对照组比较,HCST siRNA组ACHN细胞的增殖活性、侵袭能力、Bcl-2、N-cadherin和Vimentin蛋白表达水平显著降低(P＜0.05),ACHN细胞凋亡活性、caspase-3、Bax和E-cadherin蛋白表达水平显著升高(P＜0.05)。siRNA阴性对照组与对照组比较上述各指标,差异无统计学意义(P＜0.05)。结论:HCST在ccRCC中表达上调,且与ccRCC患者的免疫浸润和预后相关。沉默HCST的表达可抑制ccRCC细胞的增殖与侵袭、促进其凋亡。     

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic markerfor intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissuewas detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated byWestern blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance.Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant differencebetween ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologicdifferentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion(p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expressionof Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was anindependent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The currentstudy shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection,and it provides an important basis for screening/treating high-risk patients.