scholarly journals FOXA1 Expression in Nasopharyngeal Carcinoma: Association with Clinicopathological Characteristics and EMT Markers

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Nihel Ammous-Boukhris ◽  
Wajdi Ayadi ◽  
Mariem Derbel ◽  
Nesrine Allaya-Jaafar ◽  
Slim Charfi ◽  
...  

The forkhead box (FOXA) family of transcription factors regulates gene expression and chromatin structure during tumorigenesis and embryonic development. Until now, the relationship between FOXA1 and the nasopharyngeal carcinoma (NPC) has not yet been reported. Therefore, our purpose is to analyze the expression of FOXA1 in 56 NPC patients compared to 10 normal nasopharyngeal mucosae and to correlate the expression with the clinicopathological features. Besides, we investigated the association between FOXA1 and LMP1 gene expression, as well as the EMT markers namely the E-cadherin and Twist1. Among 56 NPC tissues, 34 (60.7%) cases were positive for FOXA1. Furthermore, we noticed that FOXA1 expression correlated with TNM (p=0.037), and age at diagnosis (p=0.05). Moreover, positive expression of FOXA1 is likely to be associated with prolonged disease-free survival and overall survival rates. On the other hand, we observed a positive association between the expression of E-cadherin and FOXA1 (p=0.0051) whereas Twist1 correlated negatively with FOXA1 (p=0.004). Furthermore, knowing that LMP1 plays a key role in the pathogenesis of NPC, we explored the association of FOXA1 with the LMP1 gene expression in both NPC cell lines and tissues. We found that, in the C666-1 which displays low levels of LMP1, the expression of FOXA1 is high, and inversely in the C15 cell line that expresses a high level of LMP1, the level of FOXA1 is low. Besides, in accordance to our results, we found that in NPC tissues there is a negative association between LMP1 and FOXA1. In conclusion, our results suggest that the overexpression of FOXA1 is associated with a nonaggressive behavior and favorable prognosis in NPC patients. FOXA1 could contribute in the EMT process through key factors as E-cadherin, Twist1, and LMP1.

2020 ◽  
Author(s):  
Mahmoud Al-Masri ◽  
Tawfiq Al-Shobaki ◽  
Hani Al-Najjar ◽  
Rafal Iskanderian ◽  
Enas Younis ◽  
...  

Abstract Introduction BRAF V600E is one of the most common mutations in Papillary Thyroid Cancer (PTC). Its clinical correlation has been extensively studied with contradictory results. The aim of this study is to evaluate the oncological impact of BRAF V600E mutation on a cohort of Middle Eastern PTC patients treated at a single institute.Methods Patients with histologically confirmed PTC that were treated surgically between 2006 to 2015 were included in the study. Formalin fixed paraffin embedded tumor blocks were sectioned and tested for BRAF V600E mutation. Short- and long-term oncological outcomes were collected. Results 128 patients (68% females) were included with a mean age of 38 years (±13.8). Median follow-up was 50 months. BRAF V600E mutation was found in 71% of patientsIThe BRAF negative tumors were significantly larger than the BRAF positive (3.47 cm versus 2.31 cm respectively, P = 0.009). All other clinicopathological characteristics were comparable between BRAF V600E mutation positive and negative groups. The two groups showed similar 5-year Disease-free (P= 0.37) and Overall survival rates (P = 0.94).Conclusion BRAF V600E mutation did not affect loco-reginal recurrence, distant metastasis, overall and disease-free survival. These results support the diversity of BRAF V600E significance among various ethnicities.


2020 ◽  
Vol 129 (10) ◽  
pp. 1011-1019
Author(s):  
Nehla Mokni Baizig ◽  
Ben Ayoub Wided ◽  
Olfa El Amine ◽  
Said Gritli ◽  
Michele ElMay

Objectives: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein–Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. Methods: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. Results: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size ( P < .001). Kaplan–Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression ( P = .018). The relationship between these two biomarkers could influence patient survival. Conclusion: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.


2020 ◽  
Vol 29 ◽  
pp. 096368972096517
Author(s):  
Changgang Guo ◽  
Ting Shao ◽  
Dadong Wei ◽  
Chunsheng Li ◽  
Fengjun Liu ◽  
...  

Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 334-334 ◽  
Author(s):  
Kanwal Pratap Singh Raghav ◽  
Wenting Wang ◽  
Michael J. Overman ◽  
Scott Kopetz

334 Background: Dysregulation of the proto-oncogene MET (mesenchymal-epithelial transition factor gene) has been implicated in tumorigenesis and correlates with worse survival and chemo/radio-resistance in colorectal cancer (CRC). EMT has been identified as a dominant molecular characteristic of a subset of CRC tumors and represents a key feature in the developing colorectal taxonomy. The purpose of this study was to compare protein expression of MET with protein/gene expression of EMT markers and other clinicopathological characteristics, and to evaluate its impact on overall survival (OS). Methods: We performed an exploratory analysis of 590 CRC samples using data from The Cancer Genome Atlas. Fisher-exact test and Pearson’s method was used to determine the relationship between MET protein expression, clinicopathological characteristics and EMT marker protein expression by reverse-phase protein array (RPPA) and EMT-associated gene expression by RNA-sequencing. Regression tree method was applied to find the best cutoff point for MET using patients with available survival data. Overall survival (OS) was estimated non-parametrically using Kaplan-Meier curve and log-rank test was used to evaluate hazard ratio. Results: MET expression by RPPA did not correlate with traditional clinicopathologic characteristics. MET was overexpressed in 17% of CRC tumors and was significantly associated with OS (HR 2.92; 95% CI: 1.45 - 5.92). Correlation analysis of MET levels with gene expression of EMT markers AXL, CDH1, FGFR1, SNAIL, TWIST1/2, VIM, SLUG, ZEB1/2, FN1 demonstrated that the highest quartile of MET protein expression was associated with a 1.5 fold increase in ZEB1 (p = 0.002), a 1.4 fold increase in AXL (p = 0.005) and ZEB2 (p = 0.008), and a 1.3 fold increase in VIM (p = 0.02). MET expression also correlated strongly with protein expressions of SNAIL (transcription factor for EMT) (r = 0.96) and ERCC1 (r = 0.83) (a marker for oxaliplatin chemo-resistance). Conclusions: Increased MET protein expression is seen in 17% of CRC tumors and strongly correlates with a molecular EMT phenotype and poor survival in patients with CRC. MET protein expression may be a surrogate biomarker for this unique subset of CRC.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 213-213
Author(s):  
Shinichiro Yamada ◽  
Mitsuo Shimada

213 Background: Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). However, several reports demonstrated the aggressive local recurrence after RFA, suggesting the induction of further malignant transformation of HCC. Methods: Eighty-eight patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for the HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and patient’s prognosis after hepatectomy were compared between the two groups. Expression levels of HIF-1, EpCAM, CD44, VEGF and EMT markers mRNA in the tumor tissues were examined. We also investigated miR-34a and miR-200c expressions in the two groups. Results: RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). The expressions of TGF-β, Twist and Snail-1 in RFA group were significantly higher than those in non-RFA group (P < 0.05), and Vimentin expression in RFA group tended to be higher than that in non-RFA group (P = 0.07). Regarding to miRNA, miR-200c and miR-34a expressions in RFA group were significantly lower than those in non-RFA group (miR-200c: P = 0.04, miR-34a: P < 0.01). Conclusions: Recurrent HCC after RFA showed the highly malignant potential through the expressions of HIF-1, cancer stem cell and EMT markers.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hsin-I Huang ◽  
Kee-Tak Chan ◽  
Chih-Hung Shu ◽  
Ching-Yin Ho

Background. Cranial nerve involvement at disease presentation of nasopharyngeal carcinoma was not uncommon. We investigated the prognosis of patients with T4-locally advanced NPC, with or without cranial nerve involvement, and compared the outcome of patients treated using different radiotherapy techniques.Methods. In this retrospective study, 83 T4-locally advanced NPC patients were diagnosed according to the seventh edition of the American Joint Committee on Cancer staging system. All patients were treated using three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT). The survival rate was analyzed using the Kaplan-Meier method.Results. The 5-year overall, locoregional-free, and disease-free survival rates of patients treated using IMRT were 88.9%, 75.2%, and 69.2%, respectively. The outcome in these patients was significantly better than that in patients treated using 3D-CRT, with survival rates of 58.2%, 54.4%, and 47.2%, respectively. There was no significant difference in the 5-year overall, locoregional-free, and disease-free survival rates of the patients with (64.2%, 60.5%, and 53.5%, resp.) and without (76.9%, 63.6%, and 57.6%, resp.) cranial nerve involvement.Conclusion. Locally advanced NPC patients treated using IMRT had significantly better outcomes than patients treated using 3D-CRT. Our results showed that the outcome of T4 NPC patients with or without cranial nerve involvement was not different.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingming Wang ◽  
Changzheng Li ◽  
Ying Liu ◽  
Zuomin Wang

Background. Laminin alpha 4 (LAMA4) is widely distributed in the basement membranes of various tissues. It can regulate cancer cell proliferation and migration. We investigated the effects of LAMA4 in gastric cancer (GC). Methods. LAMA4 expression patterns were analyzed in GC using the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Correlations between LAMA4 expression and clinicopathological characteristics were evaluated using data from The Cancer Genome Atlas (TCGA). The survival analysis was examined using the Kaplan-Meier plotter and GEPIA and ascertained by multivariate Cox analysis. Genetic alterations and DNA methylation of LAMA4 were analyzed using cBioPortal and MethSurv. LinkedOmics was applied to identify coexpressed genes of LAMA4. The association between LAMA4 and infiltration of immune cells was explored using Tumor Immune Estimation Resource (TIMER) and GEPIA. Results. LAMA4 was highly expressed in GC, and its upregulation significantly correlated with T classification ( P = 0.040 ). LAMA4 expression was an independent risk factor for overall survival (OS, P = 0.033 ). Patients with genetic alterations of LAMA4 showed a significantly better disease-free survival (DFS, P = 0.022 ). Ten CpG sites of LAMA4 were significantly associated with prognosis in GC. The functions of LAMA4 and coexpression genes were mainly involved in extracellular matrix (ECM) receptor interaction. LAMA4 expression significantly correlated with infiltration of macrophages ( P < 0.001 ), CD4+ T cells ( P < 0.001 ), and dendritic cells ( P < 0.001 ). Furthermore, LAMA4 expression was significantly associated with markers of M2 and tumor-associated macrophages (TAMs). Conclusion. LAMA4 expression was linked to GC prognosis and immune cell infiltration, indicating its potential use as a prognostic biomarker and therapeutic target.


2019 ◽  
Author(s):  
Feng-lian Yang ◽  
Yu-xia Wei ◽  
Bi-yun Liao ◽  
Gui-jiang Wei ◽  
Hai-mei Qin ◽  
...  

Abstract Background In recent years, there has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC).. We aim to delve into the position of lncRNA HOTAIR, together with EZH2, E-cadherin and H3K27me3 in NPC and explore the related mechanisms. Methods RT-qPCR and western blot analysis were carried out for detecting lncRNA HOTAIR, EZH2, E-cadherin and H3K27me3 expression in NPC tissues and cells. Moreover, the correlations between lncRNA HOTAIR and EZH2 expression and the clinicopathological characteristics and prognosis of patients with NPC were observed. NPC cell biological functions were examined through gain-of and loss-of function assays. RIP and ChIP assays were applied to detect whether lncRNA HOTAIR in NPC cells could regulate E-cadherin by recruiting EZH2 to mediate trimethylation of H3K27. Results LncRNA HOTAIR, EZH2, and H3K27me3 were richly expressed in NPC tissues and cells, and E-cadherin was lowly expressed. The prognosis of patients with overexpression of lncRNA HOTAIR and EZH2 was worse than that of patients with theirs low expression. Down-regulation of either HOTAIR or EZH2 inhibited cell proliferation, promoted apoptosis, suppressed migration and invasion and inhibited tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. Conclusion Our study suggests that lncRNA HOTAIR inhibits the expression of E-cadherin by stimulating the trimethylation of H3K27 by histone methylase EZH2 to promote cell migration, proliferation, and inhibit apoptosis of NPC cells.


Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Hyun-June Paik ◽  
Youn Joo Jung ◽  
Dong Il Kim ◽  
Seungju Lee ◽  
Chang Shin Jung ◽  
...  

<b><i>Purpose:</i></b> The <i>BRCA1/2</i> gene is the most well-known and studied gene associated with hereditary breast cancer. <i>BRCA1/2</i> genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of <i>BRCA1/2</i> mutation-positive breast cancer patients. <b><i>Methods:</i></b> The clinical data of 188 Korean breast cancer patients who underwent genetic testing of <i>BRCA1/2</i> mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of <i>BRCA1</i> and <i>BRCA2</i> mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. <b><i>Results:</i></b> The factor associated with <i>BRCA1/2</i> gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (<i>p</i> = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033–0.867), and there was a tendency to increase in stage II (<i>p</i> = 0.780; OR, 1.150; 95% CI, 0.432–3.064). <i>BRCA1</i> was significantly associated with triple-negative breast cancer (TNBC) (<i>p</i> = 0.004; OR, 5.887; 95% CI, 1.778–19.498). Gene expression of <i>BRCA2</i> was significantly reduced under 40 years of age (<i>p</i> = 0.040; OR, 0.198; 95% CI, 0.042–0.930). There was no difference in disease-free survival (<i>p</i> = 0.900) and overall survival (<i>p</i> = 0.733) between the <i>BRCA1/2</i> mutation-positive and -negative groups. <b><i>Conclusion:</i></b> In this study, the clinicopathological characteristics of breast cancer patients with <i>BRCA1/2</i> gene mutations were identified. <i>BRCA1</i> gene expression was highly correlated with TNBC. <i>BRCA1/2</i> mutation did not have a poor prognosis regarding recurrence and death.


2020 ◽  
Author(s):  
Feng-lian Yang ◽  
Yu-xia Wei ◽  
Bi-yun Liao ◽  
Gui-jiang Wei ◽  
Hai-mei Qin ◽  
...  

Abstract Background/Aim: In recent years, there has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC).. We aim to delve into the position of lncRNA HOTAIR, together with EZH2, E-cadherin and H3K27me3 in NPC and explore the related mechanisms. Methods RT-qPCR and western blot analysis were carried out for detecting lncRNA HOTAIR, EZH2, E-cadherin and H3K27me3 expression in NPC tissues and cells. Moreover, the correlations between lncRNA HOTAIR and EZH2 expression and the clinicopathological characteristics and prognosis of patients with NPC were observed. NPC cell biological functions were examined through gain-of and loss-of function assays. RIP and ChIP assays were applied to detect whether lncRNA HOTAIR in NPC cells could regulate E-cadherin by recruiting EZH2 to mediate trimethylation of H3K27. Results LncRNA HOTAIR, EZH2, and H3K27me3 were richly expressed in NPC tissues and cells, and E-cadherin was lowly expressed. The prognosis of patients with overexpression of lncRNA HOTAIR and EZH2 was worse than that of patients with theirs low expression. Down-regulation of either HOTAIR or EZH2 inhibited cell proliferation, promoted apoptosis, suppressed migration and invasion and inhibited tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. Conclusion Our study suggests that lncRNA HOTAIR inhibits the expression of E-cadherin by stimulating the trimethylation of H3K27 by histone methylase EZH2 to promote cell migration, proliferation, and inhibit apoptosis of NPC cells.


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