Glucocorticoids Suppress Renal Cell Carcinoma Progression by Enhancing Na,K-ATPase Beta-1 Subunit Expression

Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na,K-ATPase beta-subunit isoform 1 (NaK-β₁) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial-to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β₁ expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β₁ expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β₁ expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β₁ knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β₁. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β₁ cell-cell adhesion function.     

High Expression of FLOT1 Is Associated with Progression and Poor Prognosis in Hepatocellular Carcinoma

Background

The flotillin family member flotillin-1 (FLOT1) encodes a caveolae-associated, integral membrane protein that belongs to lipid raft family and involves in vesicular trafficking and signal transduction. However, the role of FLOT1 in development and progression of cancer remains largely unknown. The present study was aimed to investigate the clinical and prognostic significance of FLOT1 in hepatocellular carcinoma (HCC).

Methods

Real-time PCR and western blot analyses were applied to examine FLOT1 expression in fourteen HCC cell lines and one normal hepatic cell line, ten pairs of primary HCC and matched adjacent noncancerous liver tissues from the same patient. Immunohistochemistry (IHC) was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 196 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinical parameters.

Results

FLOT1 expression was evidently up-regulated in HCC tissues compared with that in the matched adjacent noncancerous liver tissues. In the 196 cases of tested HCC samples, FLOT1 protein level was positively correlated with Tumor size (P = 0.025), clinical stage (P<0.002), CLIP stage (P<0.001), vascular invasion (P<0.001), relapse (P<0.001), and serum AFP levels (P = 0.025). Patients with higher FLOT1 expression had shorter overall survival time, whereas those with lower FLOT1 expression had longer survival time.

Conclusions

Our study demonstrated FLOT1 is associated with aggressive characteristics of HCC, and suggested the possibility of its use as a prognostic marker in patients with HCC.     

Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1

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 p21^Cip1/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.     

Increased Expression of Pregnancy Up-Regulated Non-Ubiquitous Calmodulin Kinase Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

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.     

miR-21对肾癌细胞凋亡和侵袭力的影响

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.     

紧密连接蛋白claudin-4 在肾透明细胞癌中的表达及预后意义

目的:探讨claudin-4在肾透明细胞癌中的表达及与临床病理特征及预后的相关性。方法:应用免疫组织化学技术检测50例肾透明细胞癌组织及10例正常肾组织标本中claudin-4的表达情况,并分析与临床病理参数的相关性;随机选取其中4例肾透明细胞癌患者癌组织及4例正常肾新鲜组织,Western blot检测claudin-4的表达情况,并与免疫组化检测结果进行相关性分析;结合随访结果分析claudin-4的表达水平与患者无疾病生存期的关系。结果:Claudin-4在肾透明细胞癌组织中的表达显著高于肾正常组织(P<0.05),表达水平与肿瘤的直径、TNM分期、临床分期及淋巴结转移相关;Western blot结果也表明claudin-4在肾透明细胞癌组织中的表达显著高于肾正常组织(P<0.01),与免疫组化结果呈显著正相关(r2=0.748,P<0.01);Kaplan-Meier分析显示claudin-4高表达组患者的患者无疾病生存期为20.7个月,显著低于低表达组的30.8个月。COX多因素比例风险模型分析显示,claudin-4的表达不是肾透明细胞癌的独立预后因素(RR值=1.686,95%CI 0.174~16.311,P=0.652)。结论:claudin-4蛋白表达上调可能促进肾透明细胞癌的发生和发展,有可能作为肾透明细胞癌潜在的治疗靶点及影响不良预后的指标。     

肾细胞癌组织中PTEN和HIF-1alpha的表达及临床意义

目的：探讨PTEN和HIF-1alpha在肾细胞癌组织中的表达及临床意义。方法：随机选取2012 年1 月~2016 年1 月我院留样的 90例肾细胞癌组织（肾癌组）、90例癌旁非癌组织（癌旁组）,另选取30例非癌正常肾组织作为正常组,利用免疫组化法检测组织 中PTEN 和HIF-1alpha的表达,并分析其与肾细胞癌临床特征的关系。结果：PTEN 主要表达在细胞浆,HIF-1alpha主要表达在细胞核, PTEN、HIF-1-alpha在三组间的表达均有统计学差异（P<0.05）;PTEN高表达阳性率与Robson 分期、Fuhrman 分级、有无淋巴结转移、 有无远处转移有关（P<0.05）,HIF-1alpha高表达阳性率与Robson分期、病理分型、Fuhrman 分级、有无淋巴结转移、有无远处转移有 关（P<0.05）;PTEN表达与肾细胞癌Robson 分期和Fuhrman 分级均呈负相关（r= -0.581 , -0.442 ,P<0.05）;HIF-1-alpha表达与肾细胞癌 Robson分期和Fuhrman 分级均呈正相关（r= 0.597 ,0.489, P<0.05）;PTEN与HIF-1-alpha表达呈负相关（r=-0.435,P<0.05）。结论：PTEN 和HIF-1alpha的表达与肾细胞癌的临床分期、组织学分级以及淋巴结和远处转移等具有明显关联性,可作为提示肾细胞癌的进展的 指标。     

Fascin-1, Ezrin and Paxillin Contribute to the Malignant Progression and Are Predictors of Clinical Prognosis in Laryngeal Squamous Cell Carcinoma

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.     

High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma

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.     

VEGF和Survivin在肾癌中的表达及其相关性研究

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。     

VEGF和Survivin在肾癌中的表达及其相关性研究

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(P0.05);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。     

鞍区颗粒细胞瘤1 例的病历分析及相关文献复习

目的：探讨伴有临床症状的鞍区颗粒细胞瘤(granular cell tumour,GCT)的病理组织学起源及其治疗方法。方法：回顾性分析 我院收治的1 例具有临床症状的GCT 患者的治疗状况和病理结果,并结合近20 年来关于GCT 病理和治疗的相关文献报道,探 讨GCT 肿瘤病理组织起源和治疗要点。结果：该患者影像学报告怀疑鞍区炎性肉芽肿,给予抗生素治疗后复查MRI 显示鞍区占 位较前次无改变,增强MRI可见占位明显强化,诊断良性肿瘤,并采取翼点入路手术切除。术后病理证实为神经垂体颗粒细胞瘤。 术后患者头痛缓解,尿量、尿比重、垂体内分泌激素等相关指标相继恢复至正常值。结论：GCT 很可能起源于神经组织,伴有临床 症状的GCT 的治疗首选开颅手术,肿瘤残存的患者,术后不必放射治疗,定期复查即可。     

Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis

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.     

Enhanced Expression of ANO1 in Head and Neck Squamous Cell Carcinoma Causes Cell Migration and Correlates with Poor Prognosis

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.     

COX-2 与mPGES-1 在肾透明细胞癌中的表达及临床意义

目的:探讨环氧合酶-2(COX-2)和膜结合型前列腺素E2合成酶1(mPGES-1)在肾透明细胞癌组织中的表达及临床意义。方法:采用免疫组化SP法分别检测49例肾透明细胞癌组织标本和21例正常肾组织标本中COX-2和mPGES-1的表达。结果:COX-2在正常肾组织中的阳性表达率为4.8%,在肾透明细胞癌组织中的阳性表达率为53.1%(P<0.05);mPGES-1在正常肾组织中的阳性表达率为4.8%,在肾透明细胞癌组织中的阳性表达率为40.8%(P<0.05);COX-2和mPGES-1的高表达均与肾透明细胞癌的病理分级和临床分期无相关性(P>0.05);COX-2和mPGES-1在肾透明细胞癌中的表达呈正相关(P<0.05),r=0.5。结论:COX-2和mPGES-1在肾透明细胞癌发生及发展过程中共同发挥重要作用;COX-2和mPGES-1可能成为肾透明细胞癌新的治疗靶点。     

eEF1A1 Overexpression Enhances Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma

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.     

Expression of Ror2 Mediates Invasive Phenotypes in Renal Cell Carcinoma

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.     

ILK和VEGF165b在人肾癌组织中的表达及意义

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.     

Overexpression of EFEMP1 Correlates with Tumor Progression and Poor Prognosis in Human Ovarian Carcinoma

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.