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1.
Renal cell carcinoma (RCC) is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1), was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046), Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084) and poor prognosis in RCC patients (P = .0345). Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149) of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.  相似文献   

2.
目的:探讨miR-21对肾癌细胞凋亡和侵袭力的影响.方法:人类肾癌细胞株Caki-1和OS-RC-2细胞,分别以As-miR-21转染沉默miR-21,转染无关乱码寡核苷酸序列作阴性对照,以及不转染寡核苷酸的作空白对照,以MTT法测细胞生长,以AnnexinVFITC凋亡检测试剂盒检测凋亡,采用Transwell肿瘤浸润实验测细胞增殖力.结果:转染无关乱序miRNA的阴性对照组其细胞生存率与空白对照无差异,而转染As-miR-21的Caki-1和OS-RC-2细胞,其生存率均显著下降(P<0.05),且在72 h时生存率下降最明显;转染AS-miR-21的细胞凋亡率(Caki-1 16.7%; OS-RC-2 14.5%)相对于转染无关乱序miR-21的阴性对照细胞(Caki-12.3%; OS-RC-2 3.3%)和未转染的空白对照细胞(Caki-1 2.5%; OS-RC-2 3.7%)显著增加(P<0.05).转染AS-miR-21的细胞跨过Transwell膜的相对于转染无关乱序miR-21的阴性对照细胞和未转染的空白对照细胞显著减少(P<0.05).结论:miR-21能增加肾癌细胞的抗凋亡力和侵袭力,沉默miR-21能抑制肾癌恶性程度.  相似文献   

3.

Purpose

The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients.

Materials and Methods

The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC.

Results

The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients.

Conclusions

To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.  相似文献   

4.
PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.  相似文献   

5.

Aims

Fascin-1, ezrin and paxillin, cytoskeleton-associated proteins, have been implicated in several human cancers, but their role in laryngeal squamous cell carcinoma (LSCC) is unknown. We investigated the association of their expression and clinicopathologic factors and their prognostic value in LSCC.

Materials and Methods

Quantitative RT-PCR and western blot analyses were used to examine mRNA and protein levels in 10 fresh LSCC specimens and 10 corresponding adjacent normal margin (ANM) tissues from patients undergoing surgery in 2012. We used immunohistochemistry to retrospectively study 216 paraffin blocks of LSCC samples from patients (193 men) who had undergone surgery between 2000 and 2006 and had not received special treatment before the diagnosis. Univariate analysis of patient survival involved the Kaplan–Meier method. Multivariate analyses involved the Cox proportional hazards model.

Results

The relative mRNA and protein levels of fascin-1, ezrin and paxillin were significantly greater in LSCC than ANM tissue (P<0.05). The high expression of fascin-1, ezrin or paxillin was positively correlated with poor tumor differentiation, cervical lymph node metastasis (N+), and advanced clinical stage (III+IV) (P<0.05) but not sex or metastasis. In addition, a high expression of fascin-1 (P = 0.007) or ezrin (P = 0.047) was associated with advanced tumor stage (T3+T4). The expression of fascin-1 was higher in smokers than non-smokers (P = 0.019). A high expression of fascin-1, ezrin or paxillin was associated with poor prognosis.

Conclusions

Fascin-1, ezrin and paxillin may be prognostic of poor outcome with LSCC after surgery. Our study may lead to establishing new molecular therapeutic targets and/or prognostic biomarkers in LSCC.  相似文献   

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7.
目的:探讨肾癌组织中血管内皮生长因子VEGF与凋亡抑制蛋白Survivin表达的相关性及其之间的关系,研究Survivin和VEGF在肾癌发生发展中的作用机制。方法:应用免疫组织化学方法检测70例肾癌组织和70例癌旁正常肾脏组织中VEGF和Survivin的表达,并将检测结果与临床病理特征进行综合分析。结果:VEGF和Survivin在肾癌中表达均高于癌旁正常肾脏组织;Survivin和VEGF在肾癌中的阳性表达率分别为75.71%(53/70)和72.86%(51/70),在癌旁肾脏组织中的表达率分别为0%(0/70)、17.14%(12/70),差异均有显著性意义(P〈0.05);VEGF和Survivin的表达与患者的性别、年龄、肿瘤大小、病理分级均无相关性;VEGF和Survivin表达呈正相关性。结论:VEGF和Survivin在肾癌组织中表达率较高,为肾癌的分子靶向治疗提供了新的靶点。Survivin和VEGF在RCC中的表达关系密切,测定RCC中Survivin、VEGF蛋白的表达,有助于临床判断病人预后。  相似文献   

8.
Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07) and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS) to invasive cancer (OR=3.75; 95% CI, 1.8-7.78). Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43). Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.  相似文献   

9.
Head and neck squamous cell carcinoma (HNSCC) has the potential for early metastasis and is associated with poor survival. Ano1 (Dog1) is an established and sensitive marker for the diagnosis of gastrointestinal stromal tumors (GIST) and has recently been identified as a Ca(2+) activated Cl(-) channel. Although the ANO1 gene is located on the 11q13 locus, a region which is known to be amplified in different types of human carcinomas, a detailed analysis of Ano1 amplification and expression in HNSCC has not been performed. It is thus still unclear how Ano1 contributes to malignancy in HNSCC. We analyzed genomic amplification of the 11q13 locus and Ano1 together with Ano1-protein expression in a large collection of HNSCC samples. We detected a highly significant correlation between amplification and expression of Ano1 and showed that HNSCC patients with Ano1 protein expression have a poor overall survival. We further analyzed the expression of the Ano1 protein in more than 4'000 human samples from 80 different tumor types and 76 normal tissue types and detected that besides HNSCC and GISTs, Ano1 was rarely expressed in other tumor samples or healthy human tissues. In HNSCC cell lines, expression of Ano1 caused Ca(2+) activated Cl(-) currents, which induced cell motility and cell migration in wound healing and in real time migration assays, respectively. In contrast, knockdown of Ano1 did not affect intracellular Ca(2+) signaling and surprisingly did not reduce cell proliferation in BHY cells. Further, expression and activity of Ano1 strongly correlated with the ability of HNSCC cells to regulate their volume. Thus, poor survival in HNSCC patients is correlated with the presence of Ano1. Our results further suggest that Ano1 facilitates regulation of the cell volume and causes cell migration, which both can contribute to metastatic progression in HNSCC.  相似文献   

10.
Liver is a major contributor of protein production physiologically. The aberrant state of protein synthesis leads to tumor progression. Eukaryotic elongation factor 1 alpha 1 (eEF1A1) is a major member of the eukaryotic elongation factor family that regulates protein synthesis. Although eEF1A1 plays an essential role in controlling the cell fate, its clinical significance in tumor development and progression has not been reported. Here, we aimed to uncover the expression and prognostic significance of eEF1A1 in hepatocellular carcinoma (HCC). Our data indicated that eEF1A1 expression was elevated in HCC cell lines and clinical samples at both the mRNA and protein levels. Immunohistochemistry revealed that eEF1A1 expression was upregulated in HCC samples compared with corresponding non-tumorous tissues. In 50 HCC cases with portal vein embolus, higher eEF1A1 immunoreactivity was detected in tumor metastases compared with the primary lesions. Kaplan–Meier analysis indicated that increased eEF1A1 expression was closely associated with unfavorable post-surgical overall and disease-free survival in 453 HCC patients. Moreover, multivariate analysis indicated eEF1A1 as an independent predictor for overall and disease-free survival. Collectively, our study suggests eEF1A1 as a novel prognostic biomarker and potential therapeutic target for HCC patients.  相似文献   

11.
Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer.  相似文献   

12.
探讨整合素连接激酶(ILK)和血管内皮生长因子165b(VEGF165b)在人肾癌组织中的表达及临床意义.利用免疫组织化学S-P法检测35例肾癌组织和25例正常肾组织中ILK和VEGF165b蛋白的表达,并与肾癌临床分期进行比较.35例肾癌组织中,ILK表达率为82.9%(29/35),VEGF165b表达率为17.1%(6/35);而25例正常肾组织中ILK表达率为28.0%(7/25),VEGF165b表达率为96.0%(24/25).肾癌中ILK的表达与VEGF165b的表达呈负相关(P<0.01);ILK与VEGF165b的表达均与肾癌的临床分期有关.ILK在肾癌组织中异常活性表达,VEGF165b在肾癌组织的表达明显降低,二者表达成负相关,与肾癌的发生、发展密切相关.  相似文献   

13.

Objective

This study was to explore the role of EFEMP1 in ovarian tumor progression and its relationship with prognosis of ovarian carcinoma.

Methods

EFEMP1 mRNA and protein expressions in normal ovarian tissue, ovarian tumor, high invasive subclones and low invasive subclones were evaluated by immunohistochemistry and real time RT-PCR. Serum EFEMP1 levels in patients with ovarian tumor were measured by ELISA assay. To assess the angiogenic properties of EFEMP1, VEGF and tumor microvessel density were analyzed in ovarian carcinoma by immunohistochemistry.

Results

EFEMP1 expression was up-regulated in ovarian carcinoma, positively correlated with MVD and VEGF, and its overexpression and high serum levels were significantly associated with high stage, low differentiation, lymph node metastasis and poor prognosis of ovarian cancer. EFEMP1 expression was also found to be over-expressed in the highly invasive subclones compared with the low invasive subclones.

Conclusion

EFEMP1 is a newly identified gene over-expressed in ovarian cancer, associated with poor clinicopathologic features and promotes angiogenesis. This study shows that EFEMP1 may serve as a new prognostic factor and a therapeutic target for patients with ovarian cancer in the future.  相似文献   

14.
G Yu  W Yao  J Wang  X Ma  W Xiao  H Li  D Xia  Y Yang  K Deng  H Xiao  B Wang  X Guo  W Guan  Z Hu  Y Bai  H Xu  J Liu  X Zhang  Z Ye 《PloS one》2012,7(8):e42377

Background

Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray.

Methodology/Principal Findings

With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 17157. From the data we found there were thousands of lncRNAs that differentially expressed (≥2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs differentially expressed in five or more of six RCCC samples. Compared with NT, many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data showed that down-regulated lncRNAs were more common than up-regulated ones. ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty-three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in RCCC compared with matched histologically normal renal tissues.

Conclusions/Significance

Our study is the first one to determine genome-wide lncRNAs expression patterns in RCCC by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples, which revealed that lncRNAs differentially expressed in tumor tissues and normal tissues may exert a partial or key role in tumor development. Taken together, this study may provide potential targets for future treatment of RCCC and novel insights into cancer biology.  相似文献   

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17.
王磊  熊英  李军  马俊文  陈申思 《生物磁学》2013,(35):6904-6906
目的:探讨胃癌外周血中树突状细胞CD83+表达对预后的影响及意义。方法:选取2010年1月至2011年6月间我科收治的胃癌病人74例进行分析,均为原位癌或仅有局部淋巴结转移,以外周血树突状细胞CD83+为研究对象,以术后生存时间为标准,对病人手术预后进行分析。结果:所选74例病人术后3周测得外周血树突状细胞CD83+表达频数平均值(7.32+1.88脚,以表达频数中位数7.32%为标准将74例病人分为高频组和低频组两组,每组37人。术后总体生存时间108周-413周,平均生存时间(207+227)周,其中高值组平均生存时间(247+121)周,低值组平均生存时间(118+54)周,两组生存时间具有明显差别(P〈O.05)。结论:胃癌外周血中树突状细胞CD83+的表达对接受手术病人预后有重要影响,可以作为判断病人预后的参考依据,对预后不良者加以对症及时干预以降低死亡率。  相似文献   

18.
19.
ObjectiveThis study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC.ConclusionsThis study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429) may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.  相似文献   

20.
With new frontiers of pharmaceutical therapies focusing on tumor growth and angiogenesis, understanding the interaction between immune system and tumor microenvironment has become ever more important. Chemokines and chemokine receptors appear to play an integral role in tumor characteristics. Evidence suggests CXCR4, CXCL5, CXCR7, and stromal derived factor-1 appear to be crucial in survival, growth, and metastasis of renal cell carcinoma. As the role of chemokines in renal cancer is becoming more evident, further research will lead to a better understanding of tumor biology and the development of new therapeutic targets to help improve survival.Key words: Chemokine, Cytokines, Renal cell carcinoma, OncocytomaRenal cell carcinoma (RCC) is the seventh most common malignant condition among men and twelfth among women, representing 2% to 3% of all cancers.1 Thirty to 40% of affected patients present with stage III or stage IV disease. It has an estimated incidence of 57,760 per year, which has increased 2% to 3% per year with no significant decrease in mortality rates.2 Median survival of patients with metastatic disease is merely 13 months.1 Studies have established that tumor and stroma interact through a variety of cytokines, chemokines, and growth factors.3 Recent evidence suggests chemokines may facilitate tumor growth, survival, and metastatic potential of various cancers including RCC. Chemokines have a potential to be utilized as tumor markers and novel targets of antiangiogenic therapy. Investigating the role of various chemokines in the development and metastasis of cancer has become a major focus of contemporary research. We examined the relevant literature and present a review of selected chemokines and their roles in renal cell cancers.  相似文献   

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