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1.

Objectives

Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality in the world. Accumulating evidence has highlighted the regulatory roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in HCC.

Methods

The lncRNA expression data and corresponding patient information were obtained from The Cancer Genome Atlas (TCGA) database. Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis was implemented using the Spearman correlation coefficient. Multivariate Cox regression survival analysis was utilized to extract prognostic lncRNAs in the network.

Results

Based on the “ceRNA hypothesis”, a global lncRNA-associated ceRNA network (LCeNET) in HCC was constructed. Nine lncRNAs were identified as hubs and found to be enriched in various cancer-related biological processes. In addition, ceRNA pairs associated with survival were screened to construct a lncRNA-miRNA-mRNA sub network. Finally, we developed a sixteen-lncRNA model that could classify patients into high- and low-risk subgroups with different survival outcomes, and MCM3AP-AS1 functioned as a hub in both LCeNET and prognostic model.

Conclusions

Our work will improve the understanding of lncRNA-mediated ceRNA regulatory mechanisms in HCC pathogenesis and facilitate the identification of candidate prognostic biomarkers for HCC.  相似文献   

2.

Background

Hypoxia inducible factor 1α (HIF-1α) is a protein related with carcinogenesis and metastasis in many tumors. However, little is known about the prognostic value of HIF-1α in hepatocellular carcinoma (HCC) patients with cirrhosis.

Methods

Clinical-pathological information and follow-up data were collected from HCC (n?=?419) and chronic hepatitis (n?=?49) patients. HIF-1α expression was scored based on the percentage of immunohistochemical staining. Correlations between HIF-1α expression and clinical features were evaluated by Chi-square test. And survival analysis was performed by multivariate Cox regression analysis.

Results

In cirrhosis patients, the frequency of HIF-1α positive expression in HCC was higher than in chronic hepatitis (P?=?0.002). HIF-1α positive expression was significantly associated with vascular invasion (P?=?0.002), TNM stage (P?=?0.005), HBV infection (P?=?0.005), tumor size (P?=?0.025) and portal vein tumor thrombus (P?=?0.001) in HCC with liver cirrhosis. While, in cirrhosis-free patients, HIF-1α positive expression had a significant correlation with vascular invasion (P?=?0.039) and AFP value (P?=?0.001) in. HIF-1α “positive” had decreased overall survival compared to HIF-1α “negative” patients and this was an independent adverse prognostic factor (multivariable analysis P?=?0.001) for HCC patients with cirrhosis, but not for cirrhosis-free patients.

Conclusions

Our results suggested that HIF-1α served as a poor prognostic factor for HCC patients with cirrhosis.  相似文献   

3.

Objective

Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. Alkaline ceramidase 3 (Acer3) hydrolyzed long-chain unsaturated ceramide to produce free fatty acids and sphingosine. However, whether and how Acer3 modulates progression of HCC remains largely unknown.

Methods

Acer3 mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database. The expression level of Acer3 in human HCC cell lines were examined by western blot. Overall survival and disease-free survival of HCC patients were determined by Kaplan-Meier analysis. Effects of Acer3 knockdown by lentivirus infection were evaluated on cell growth and apoptosis. The mechanisms involved in HCC cells growth and apoptosis were analyzed by western blot.

Results

In silico analysis of TCGA databases of HCC patients showed that the expression of Acer3 significantly inversely correlates with the overall and disease-free survival of HCC patients. Knockdown expression of Acer3 resulted in decreased cell growth and increased apoptosis. Notably, inhibition of Acer3 resulted in intracellular exhaustion of Sphingosine-1-phosphate (S1P) and inhibited activation of S1PR2/PI3K/AKT signaling. Finally, knockdown of Acer3 induced up-regulation of Bax and down-regulation of Bcl-2.

Conclusions

Our study suggests that Acer3 contributes to HCC propagation, and suggests that inhibition of Acer3 may be novel strategy for treating human HCC.  相似文献   

4.

Background

We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers.

Methods

We immunohistochemically assessed expression levels of the cell-cycle regulators Rb1, p16 and cyclin-dependent kinase 4 (CDK4), and the DNA repair enzymes O6-methylguanine-DNA-alkyltransferase (MGMT) and flap endonuclease-1 (FEN1) separately in malignant tissue and benign tissue from resection margins in 102 cases of PDAC. Nearly all (95.1%) patients had undergone pancreaticoduodenectomy.

Results

The studied proteins showed wide but somewhat variable expression in both benign and malignant pancreatic tissues. Strong CDK4 expression in islets of Langerhans predicted poor relapse-free survival (RFS) (HR 2.874; 95% CI 1.261–6.550; p?=?.012) and within T3–4 tumors CDK4 expression in adenocarcinoma cells also predicted poor disease-free survival (DFS) (RR 2.148; 95% CI 1.081–4.272; p?=?.029). Strong MGMT expression was associated in N1 patients with weak local relapse-free survival (RFS), DFS and overall survival; all significantly in Cox regression analysis. FEN1 was also an independent predictor of decreased DFS (in the whole study population) and worse RFS (in the patients with T3–4 tumors).

Conclusions

Major cell-cycle regulator also have predictive significance, but further studies are required to evaluate this.  相似文献   

5.

Objective

To evaluate the expression and prognostic significance of ALDH1A1 in gastric neuroendocrine carcinoma.

Materials and methods

Immunohistochemical stains of ALDH1A1 were evaluated in 67 cases of gastric neuroendocrine carcinoma. The findings were correlated with clinicopathologic variables and overall survival.

Results

Immunohistochemistry revealed positive cytoplasmic immunoreactivity in 35 of 67 (52.2%) tumors and strongly positive immunoreactivity in 14 of 67 (20.9%). Strongly positive ALDH1A1 expression, but not positive staining, was significantly associated with lymph node status, lymphovascular invasion, and ki-67 index (P = 0.039, 0.045, and 0.045, respectively). Kaplan‐Meier survival curves and log-rank tests showed significantly poorer prognoses in cases of high ALDH1A1 expression compared to cases of low ALDH1A1 expression or the negative control group (MST, 17 vs. 52 months; P = 0.026). Multivariate analysis showed that high ALDH1A1 expression, lymph node metastasis, and lymphovascular invasion had significant associations with decreased overall survival (P = 0.029, 0.008, and 0.005, respectively).

Conclusions

High ALDH1A1 expression may be a prognostic indicator of survival in patients with gastric neuroendocrine carcinoma.  相似文献   

6.

Objective

to evaluate the prognostic value of base excision repair proteins in sporadic colorectal cancer.

Methods

Pre-treatment tumor samples from 72 patients with sporadic colorectal adenocarcinoma were assessed for APC, MPG, Polβ, XRCC1 and Fen1 expression by immunohistochemistry. The associations of molecular data were analyzed in relation to clinical features and TNM staging as a prognosis predictor and disease-free survival.

Results

Higher levels of MPG, Polβ and XRCC1, but not Fen1, were associated with unfavorable pathological outcomes, such as poor cellular differentiation, advanced TNM stages, presence of lymphatic and perineural invasions and metastatic lymph nodes. MPG and Polβ overexpression were associated with right-sided CRC. However, only MPG high expression is associated with shorter disease-free survival in CRC patients.

Conclusions

Our results suggest that increased expression of MPG, Polβ and XRCC1 are more likely to evolve to poor pathological outcomes, but only the elevated expression of MPG protein predicts recurrence. The BER proteins appear to be suitable candidates to refine the TNM current staging of colorectal cancer.  相似文献   

7.

Background

The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer.

Methods

Paraffin-embedded resected tissues of gastric cancer mucosa (n?=?436) and adjacent normal mucosa (n?=?92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated.

Results

The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P?<?0.01).

Conclusion

MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.  相似文献   

8.

Background

To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients.

Methods

Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated.

Results

In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2–3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3–7.6], p?=?0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3–7.7], p?=?0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4–12.8], p?<?0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p?=?0.560) or overall survival (p?=?0.799).

Discussion

Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.  相似文献   

9.

Objective

The aim of this study was to determine the clinicopathological significance and potential prognostic role of SIRT1 expression in colorectal cancer (CRC) using immunohistochemistry and meta-analysis.

Methods

Immunohistochemistry was performed on 265 archival paraffin-embedded human CRC specimens to investigate the correlation between SIRT1 expression and clinicopathological characteristics, including patient survival. To elucidate the potential prognostic value of SIRT1 expression, a meta-analysis was performed using data on 2132 patients from eight eligible studies.

Results

SIRT1 was highly expressed in 24.5% of the 265 CRC specimens analyzed. High SIRT1 expression correlated with vascular invasion (P?=? 0.041). High SIRT1 expression also significantly correlated with expression of SNAI (P?=? 0.001), but not E-cadherin (P?=? 0.958). However, there was no significant correlation between SIRT1 expression and other clinicopathological parameters. High SIRT1 expression in the CRC specimens significantly correlated with a worse overall survival rate, independent of SNAI expression. However, based on the meta-analysis, high SIRT1 expression was not significantly correlated with overall survival rates [hazard ratio (HR) 1.111, 95% confidential interval (CI) 0.799–1.544].

Conclusion

In our retrospective study, high SIRT1 expression significantly correlated with vascular invasion and a worse prognosis. However, because the results from the meta-analysis differed the retrospective arm of our study, additional cumulative studies are needed to determine the prognostic value of SIRT1 in CRC.  相似文献   

10.

Background

Allergic diseases can expand at any age as a result of complicated interaction of environmental and genetic factors. Through the years, studies have found that allergic diseases are primarily described by elevated Th2 pathway activation, leading to increased serum IgE levels, allergen reactivity, blood eosinophil counts and secreted interleukins.

Methods

A total of 20 patients with allergy and 20 matched controls participants were recruited for the study. A study was designed with the framework of an ongoing project at the Regional Children's Hospital in Olsztyn on the analysis of the immune profile of children with allergy and asthma. Diagnosis was conducted by medical specialists. Whole blood samples were collected and serum IL’s and chemokin levels were made using ELISA kits.

Results

Results demonstrated that in comparison to the controls, the individuals with allergy showed significantly higher concentration of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13 and TNF-α. We also demonstrated significant correlations between the levels of cytokines which implies the presence of an interactive network between them. The results of ROC analysis indicated the 3-factors (IL-1β, IL-4, IL-8) could be additional, helpful biomarkers in better diagnosis of allergy.

Conclusions

In this study, serum levels of cytokine differed among children with allergy. However, the findings of this support the possibility of using an appropriate selection of serum cytokine for the diagnosis allergy and emphasize the need to standardize quantitative methods for serum analysis.  相似文献   

11.

Objective

To test the impact of a redesigned, patient-centered after visit summary (AVS) on patients’ and clinicians’ ratings of and experience with the document.

Methods

We conducted a difference-in-differences (DiD) evaluation of the impact of the redesigned AVS before and after its introduction in an academic primary care practice compared to a concurrent control practice. Outcomes included ratings of the features of the AVS.

Results

The intervention site had 118 and 98 patients in the pre- and post-intervention periods and the control site had 99 and 105, respectively. In adjusted DiD analysis, introduction of the patient-centered AVS in the intervention site increased patient reports that the AVS was an effective reminder for taking medications (p?=?.004) and of receipt of the AVS from clinicians (p?=?.002). However, they were more likely to perceive it as too long (p?=?.04). There were no significant changes in overall rating of the AVS by clinicians or their likelihood of providing it to patients.

Conclusions

A patient-centered AVS increased the number of patients receiving it and reporting that it would help them remember to take their medications.

Practice implications

Improvements in the patient-centeredness of the AVS may improve its usefulness as a document to support self-management in primary care.  相似文献   

12.

Objectives

A lack of focus on variation in engagement among cancer populations of differing developmental stages led us to examine the associations between patient engagement, the patient-provider relationship, cognitive development, readiness to transition to adulthood (transitional readiness) and perceived quality of care.

Methods

A sample of 101 adolescent cancer patients (diagnosed 10–20 years) completed survey items concerning patient engagement, dimensions of the patient-provider relationship, cognitive development, transitional readiness, and demographic characteristics using an iPad/tablet during a routine clinic visit.

Results

Patient engagement was not significantly associated with perceived quality of care (b?=?.02, 95% CI: ?0.06, 0.11). Instead, adolescents with providers that supported their independence (b?=?.34, 95% CI: 0.17, 0.52) were significantly more likely to perceive higher quality care.

Conclusion

Supportive patient-provider relationships are an integral part of adolescents’ perceptions of quality of care. Adolescents are still gaining important skills for navigating the medical system, and the patient-provider relationship may provide an important scaffolding relationship to help adolescents build independence in their treatment experience.

Practice implications

Identifying potential mechanisms through which adolescents can provide their opinion, ask questions, and participate in their treatment plan will help in supporting adolescent independence and improve quality of care.  相似文献   

13.

Objective

Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC.

Methods

A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed.

Results

The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC.

Conclusion

This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.  相似文献   

14.

Background and aim

Nucleolar and spindle-associated protein 1 (NUSAP1) is an indispensable mitotic regulator. Aberrant NUSAP1 expression is associated with perturbed mitosis and tumorigenesis. In this study, we investigated the clinical significance of NUSAP1 expression in colon cancer.

Methods and materials

Immunohistochemical staining was performed to determine NUSAP1 protein levels in paraffin colon tumor specimens. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was conducted to detect NUSAP1 mRNA levels in colon tumor samples. The association between NUSAP1 protein expression and clinicopathological characteristics of patients with colon cancer was assessed. A Kaplan-Meier analysis was performed to determine the prognostic significance of NUSAP1 in colon cancer. A Cox proportional hazards model was used to calculate univariate and multivariate hazard ratios for the NUSAP1 and other clinicopathological variables.

Result

NUSAP1 protein and mRNA levels were significantly higher in colon tumor tissues than in paired non-cancerous adjacent tissues (P?<?0.001, respectively). NUSAP1 protein expression was significantly correlated with histopathological grading (P?<?0.001), depth of invasion (P?=?0.001), lymph node metastasis (P?<?0.001) and TNM stage (P?<?0.001). The overall survival rate of patients with high NUSAP1 expression was significantly lower than for patients with low NUSAP1 expression (log-rank test, P?<?0.001). A multivariate Cox model demonstrated that NUSAP1 is an independent risk factor for overall survival (P?=?0.025).

Conclusion

NUSAP1 is overexpressed in colon cancer and high expression of NUSAP1 acts as an independent predictive factor for poor prognosis in colon cancer.  相似文献   

15.
16.

Introduction

Gastric hepatoid carcinomas (GHCs) include type I (classic) and type II (fetal type gastrointestinal adenocarcinoma). The classic type shows overlapping morphologic features with those of hepatocellular carcinoma (HCC). The aim of this study is to investigate expression of LIN28 in GHCs and explore its utility to distinguish classic GHC from HCC.

Methods

We investigated immunohistochemical expression of LIN28 in 93 primary GHCs (47 type I, 46 type II) and 60 HCCs with comparison to SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7. We also stained LIN28 and SALL4 in 52 conventional gastric adenocarcinomas to assess their specificity in gastric carcinomas.

Results

Classic GHCs and fetal type gastrointestinal adenocarcinomas showed positive LIN28 in 21/47 (45%) and 10/46 (22%), SALL4 in 41/47 (87%) and 36/46 (78%), AFP in 30/46 (65%) and 33/46 (72%), glypican-3 in 31/41 (76%) and 24/38 (63%), Hep Par1 in 27/41 (66%) and 28/37 (76%), and CK7 in 15/40 (38%) and 25/38 (66%), respectively. p-CEA staining was seen in 19/44 (43%) classic GHCs. Among HCCs, LIN28, SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7 was seen in 1/60 (2%), 0/60 (0%), 6/30 (20%), 23/30 (77%), 29/30 (97%), 28/30 (93%) and 21/30 (70%) cases, respectively. LIN28 and SALL4 staining was seen in 2/52 (4%) and 14/52 (27%) gastric conventional adenocarcinomas, respectively. The sensitivity and specificity of distinguishing classic GHCs from HCCs was 45% and 98% for LIN28, 87% and 100% for SALL4, 65% and 80% for AFP, 76% and 30% for glypican-3, 66% and 3% for Hep Par1, 43% and 7% for p-CEA, and 38% and 30% for CK7, respectively. Combining LIN28 and SALL4 increased the sensitivity to 96% with 98% specificity to distinguish classic GHCs from HCCs.

Conclusions

LIN28 is a very specific marker (98% specificity) for distinguishing classic GHCs from HCCs though it is not as sensitive as SALL4. AFP, glypican-3, Hep Par1 and p-CEA are not useful in distinguishing classic GHCs from HCCs. Combining LIN28 and SALL4 increased the sensitivity to distinguish classic PHCs from HCCs.  相似文献   

17.

Background

It was found that G-protein-coupled receptor kinase 3 (GRK3) played key biological roles in some cancers. However, its associations with clinicopathologic features and prognosis in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

Methods and methods

Expression of GRK3 was detected, using tissue microarray-based immunohistochemistry, in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 165 patients with PDAC after curative resection, and was further correlated with clinicopathologic parameters and cancer-specific survival (CSS).

Results

It was shown that GRK3 expression was much lower in tumor than in non-tumor tissues. Moreover, expression of GRK3 in tumor tissues was significantly associated with gender and T stage. Univariately, high GRK3 expression was predictive for favorable CSS, along with some conventional clinicopathologic variables. In multivariate Cox regression test, GRK3 expression remained to be a significant prognostic marker for PDAC. Finally, combination of GRK3 with some clinicopathologic variables, especially N stage, obtained more precise prediction for CSS.

Conclusions

Our data suggested that expression of GRK3 was down-regulated in PDAC and was an independent prognostic factor.  相似文献   

18.

Background

Patients with type I diabetes are at increased risk of osteoporosis even after insulin therapy in adult stage. This study was conducted to compare the efficacy of hesperidin (hesp) therapy versus that of insulin alone in the alleviation of osteoporosis arising from type I diabetes mellitus (T1DM) in young rats.

Materials and methods

Hesperidin was administered orally to STZ-induced diabetes. The animals were evaluated morphologically and biochemically and compared with that received daily SC injections of long-acting insulin.

Results

Histologically, we observed the degeneration of osteoblasts and osteocytes, decreased collagen fibers, and disturbed bone turn over markers in untreated DM rats. Hesperidin+ insulin supplementation to diabetic rats caused significant improvement of most of the bone histological and morphometric parameters compared with the insulin-treated group. Furthermore, hesp treatment significantly reduced pro-inflammatory mediators TNFα and NF-κB and increased serum biochemical markers of bone turnover, including osteopontin (OPN), osteocalcin (OC) and decreased serum alkaline phosphatase (ALP).

Conclusion

These data demonstrated that hesp could be considered to be a beneficial drug for preventing diabetic osteoporosis in growing age.  相似文献   

19.

Objective

To document the effect of a cancer specific question prompt list (QPL) on patients question asking and shared decision-making (SDM), and to evaluate the combined effect of the QPL and consultation audio recording (CAR) on patient outcomes.

Method

This exploratory study compared two groups of patients receiving either a QPL or combined QPL/CAR, to a control group. Measurements included number/types of questions asked, and physician SDM behavior (OPTION score). Questionnaire data included anxiety/depression and quality of life (QoL).

Results

A total of 93 patients participated (31 Control, 30 QPL and 32 Combined). Patients in the intervention groups asked more questions concerning prognosis (p?<?.0001), the disease (p?=?.006) and quality of treatment (p?<?.001) than patients in the control group, but no impact was found on the OPTION score. An increase in mean consultation length was observed in the intervention groups compared to the control group (44 vs. 36?min; p?=?.028). Patients rated both interventions positively.

Conclusion

Provision of the QPL facilitates patients to ask a broader range of questions, but does not increase physician SDM behavior.

Practical implementation

The combination of QPL and CAR seems feasible and should be tested in an implementation study following the disease trajectory.  相似文献   

20.

Background

Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane.

Aim

Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data.

Methods

We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC.

Results

Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p?=?0.004 and p?<?0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p?=?0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p?=?0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p?=?0.002?=?0.010 and <0.001 respectively), distant metastases (p?=?0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p?<?0.001 and p?=?0.013 respectively).

Conclusion

Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.  相似文献   

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