Epithelial-Mesenchymal Transition Markers β-catenin, Snail, and E-Cadherin do not Predict Disease Free Survival in Prostate Adenocarcinoma: a Prospective Study

2015 ◽  
Vol 21 (4) ◽  
pp. 1209-1216 ◽  
Author(s):  
Tumay Ipekci ◽  
Ferhat Ozden ◽  
Betul Unal ◽  
Caner Saygin ◽  
Didem Uzunaslan ◽  
...  
2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 693-693
Author(s):  
Jun-Eul Hwang ◽  
Woo Kyun Bae ◽  
Hyun-Jeong Shim ◽  
Sang-Hee Cho ◽  
Ik-Joo Chung

693 Background: BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer. Methods: A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in three independent cohorts (GSE 17536, GSE 14333, and GSE 39582). Results: The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation type colorectal cancer was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.0355), poor disease-free survival (P = 0.00794), and poor disease-specific survival (P = 0.0341) in GSE 17536. In GSE 39582, BRAF mutation type colorectal cancer demonstrated the trend of poor overall survival according to increase of stage. In a multivariate analysis, BRAF mutation gene signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.7; 95% CI 1.59-2.83: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition and colon cancer metastasis signaling are the possible explanations for poor prognosis of BRAF mutation type colorectal cancer. Conclusions: BRAF mutation signature is highly associated with poor prognosis in colorectal cancer, especially in advanced stage, and the molecules associated with epithelial-mesenchymal transition can be potential therapeutic targets in BRAF mutation type colorectal cancer.


2014 ◽  
Vol 37 (5) ◽  
pp. 320 ◽  
Author(s):  
Desirée Hao ◽  
Tien Phan ◽  
Amanda Jagdis ◽  
Jodi E Siever ◽  
Alexander C Klimowicz ◽  
...  

Purpose: Aberrant expression of proteins involved in epithelial-to-mesenchymal transition have been described in various cancers. In this retrospective study, we sought to evaluate E-cadherin, β-catenin and vimentin protein expression in non-metastatic nasopharyngeal (NPC) patients treated with curative intent, examine their relationship with each other, and with clinical outcome measures. Methods: Pre-treatment formalin-fixed paraffin-embedded biopsies of 140 patients treated between January 2000 and December 2007 were assembled into a tissue microarray (TMA). Automated quantitative immunohistochemistry (AQUA®) was performed on sequential TMA sections stained with fluorescent-labeled antibodies against E-cadherin, β-catenin and vimentin. Cox proportional hazards regression was used to estimate the effect of cytoplasmic vimentin, cytoplasmic E-cadherin, β-catenin nuclear/cytoplasmic ratio expression on overall survival and disease-free survival. Results: The average age of the patients was 51.7 years (SD=12.1; range 18-85), 66% were male, 71% had a KPS ≥ 90% at the start of treatment and 65% had stage III/IV disease. After adjusting for performance status, WHO and stage, high E-cadherin levels over the 75th percentile were found to produce a significantly increased risk for both a worse overall survival (HR = 2.53, 95% CI 1.21, 5.27) and disease free survival (DFS; HR = 2.14, 95%CI 1.28, 3.59). Vimentin levels over the first quartile produced an increased risk for a worse DFS (HR = 2.21, 95% CI 1.11, 4.38). No association was seen between β-catenin and survival. Conclusion: In this cohort of NPC patients, higher levels of E-cadherin and higher levels of vimentin were associated with worse outcomes. Further work is needed to understand the role of these epithelial mesenchymal transition proteins in NPC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Cheng ◽  
Linxiang Zhou ◽  
Yalan Long ◽  
Juanjuan Xiang ◽  
Longhua Chen

BackgroundGiven the reported correlation between the oncogene metastasis-associated in colon cancer 1 (MACC1) and nasopharyngeal carcinoma (NPC), as well as between MACC1 and epithelial–mesenchymal transition (EMT), we speculated that EMT is a likely causative link between MACC1 expression and poor NPC prognosis. Thus, we aim to clarify the relationship between MACC1 and EMT in NPC prognosis.Material and MethodsWe performed immunohistochemical examination of tissue sections from 128 NPC patients that were divided into six groups corresponding to high and low protein expression of MACC1 and two EMT-related proteins, vimentin and E-cadherin, and Kaplan–Meier (KM) survival analyses were performed.ResultsKM survival analysis showed that upregulation of MACC1 and vimentin and downregulation of E-cadherin were significantly associated with reduced survival in NPC. Short hairpin RNA (shRNA) interference and immunoblotting in the NPC cell line HNE-1 led to increased E-cadherin but decreased vimentin levels. MACC1 overexpression was significantly correlated with poor 5-year overall survival, metastasis-free survival, and disease-free survival (P<0.05) but not with poor relapse-free survival (P>0.05). Univariate analyses revealed that MACC1, E-cadherin, and vimentin levels along with T and N tumor classifications and cancer staging are significant prognostic factors of NPC (P<0.05).ConclusionOur findings showed the association between MACC1 and EMT in NPC malignancy and support the role of MACC1 as a prognostic biomarker and molecular target for NPC treatment.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yaodu Wang ◽  
Zhiyang Wu ◽  
Likuan Hu

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.


2019 ◽  
Vol 34 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Gino Marioni ◽  
Lorenzo Nicolè ◽  
Rocco Cappellesso ◽  
Rosario Marchese-Ragona ◽  
Elena Fasanaro ◽  
...  

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of β-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. Methods: The expression of β-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. Results: Statistical analysis showed no significant associations between β-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and β-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). Conclusions: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and β-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how β-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.


2002 ◽  
Vol 20 (7) ◽  
pp. 1775-1785 ◽  
Author(s):  
Ronnie Tung-Ping Poon ◽  
Irene Oi-Lin Ng ◽  
Cecilia Lau ◽  
Wun-Ching Yu ◽  
Zhen-Fan Yang ◽  
...  

PURPOSE: This study prospectively evaluated the correlation of tumor microvessel density (MVD) with clinicopathologic features and postoperative recurrence in patients undergoing resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Tumor MVD was assessed in 100 patients with resection of HCC using a computer image analyzer after immunostaining for CD34 (MVD-CD34) and von Willebrand factor (MVD-vWF), respectively. Patients were prospectively followed for recurrence. RESULTS: Mean tumor MVD-CD34 (236/0.74 mm2) was higher than mean tumor MVD-vWF (87/0.74 mm2) (P < .001). By multiple regression analysis, tumor size was the only pathologic feature significantly related to tumor MVD-CD34. The median MVD-CD34 was 316/0.74 mm2 in HCCs ≤ 5 cm (n = 46) and 146/0.74 mm2 in HCCs more than 5 cm (n = 54) (P < .001). Among patients with HCCs ≤ 5 cm, those with higher than median MVD-CD34 had worse disease-free survival (at 3 years, 13%) than those with a lower MVD-CD34 (at 3 year, 74%) (P = .002). Multivariate analysis showed that tumor MVD-CD34 was the only significant factor predictive of disease-free survival in patients with HCC ≤ 5 cm. For HCCs more than 5 cm, MVD-CD34 did not have a significant prognostic influence. MVD-vWF did not have a significant prognostic influence on disease-free survival in either HCCs ≤ 5 cm or more than 5 cm. CONCLUSION: This study shows that a high MVD-CD34 was predictive of early postresection recurrence in patients with HCCs ≤ 5 cm and, therefore, may be a novel prognostic marker in this subset of patients.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9542-9542 ◽  
Author(s):  
E. Braggio ◽  
D. P. Guimaraes ◽  
C. E. Bacchi ◽  
L. F. Lopes ◽  
I. A. Small ◽  
...  

9542 Background: To search for markers for better prognostic evaluation in patients (pts) with GIST was our goal. Loss of E-cadherin expression and/or function by hypermethylation has been correlated with increase in the invasive potential of human tumors. Recently, loss of p16INK4a expression was considered as an independent prognostic factor in pts with GIST. Methods: We investigated the methylation (MT) status for p16Ink4a and E-cadherin by the MT -specific PCR, c-KIT mutation by SSCP-sequencing, p16INK4a and cKIT expressions and KI-67 index by IHC, in 81 pts with completely ressected GIST between Jan 1990 and April 2003. Clinical data and follow-up information were obtained from medical records.A cutoff at 20% and 5% positivity was used for p16INK4a and KI-67, respectively. Univariate analysis of disease-free survival (DFS) and overall survival (OS) were performed by Kaplan Meier method with the log-rank test. Results: Median age was 55 (9–78); Male/female 42/58%; primary tumor sites were stomach (46.9%), small bowell (37.0%), colorectal (8.6%) and peritoneal (6.2%). Median tumor size was 8cm (1.2–35.0). The median follow-up was 24 months. Pts were stratified into low- (24.7%), intermediate- (37.0%) and high- (38.3%) risk pts based on tumor size and mitotic index. There was a significant correlation between risk classification and disease free survival (DFS) (p=0.023) and overall survival (OS) (p=0.010). The p16Ink4a and E-cadherin MT were observed in 19.4% and 63.3% pts, respectively. We observed loss of p16INK4a expression in 64.9% of GISTs. Overall, 78.4% had KIT mutation in exon 11 or 9. There was non-significant correlations between epigenetic alterations, cKIT mutation, p16INK4a expression, KI-67 index and survival. By analysing the three groups separately we found a significant correlation between E-cadherin MT with DFS (p<0.047) only in the intermediate risk group. Conclusion: Our results suggest that E-cadherin MT may be a helpful prognostic factor particularly in the intermediate risk group of GISTs. In contrast with previous results from the literature p16INK4a alterations had no prognostic impact in our samples. No significant financial relationships to disclose.


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