scholarly journals Overexpression of UBE2C in esophageal squamous cell carcinoma tissues and molecular analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rong Li ◽  
Xing-Feng Pang ◽  
Zhi-Guang Huang ◽  
Li-Hua Yang ◽  
Zhi-Gang Peng ◽  
...  

Abstract Background Esophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC). Methods In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C. Results UBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51–2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90–0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C). Conclusion UBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shirui Chen ◽  
Kai Zhou ◽  
Liguang Yang ◽  
Guohui Ding ◽  
Hong Li

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.


2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Zhiming Dong ◽  
Shengmian Li ◽  
Xuan Wu ◽  
Yunfeng Niu ◽  
Xiaoliang Liang ◽  
...  

AbstractNatural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5′-mc to 5′-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients’ survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.


Rare Tumors ◽  
2020 ◽  
Vol 12 ◽  
pp. 203636132097221
Author(s):  
Jason Starr ◽  
Brian Ramnaraign

The most common associated malignancies with BRCA mutations include breast and ovarian cancers. Less common malignancies associated with BRCA mutation include: pancreatic, prostate, colon, gastric, and biliary cancers. Esophageal cancer, particularly squamous cell carcinoma, has rarely been reported to harbor BRCA mutations. Here we report, to our knowledge, the first case of germline BRCA1 mutated associated esophageal squamous cell carcinoma.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13649-e13649
Author(s):  
Tatiana P. Protasova ◽  
Natalya N. Timoshkina ◽  
Evgeniy N. Kolesnikov ◽  
Mikhail A. Averkin ◽  
Umar Muhmadovich Gaziev ◽  
...  

e13649 Background: The survival of patients with esophageal squamous cell carcinoma depends not only on clinical signs (TNM, tumor site), but also on the molecular genetic subtype of the tumor. Identification of the molecular genetic subtype and the presence/absence of clinically significant mutations is an important step towards finding new effective drugs and choosing the most appropriate therapeutic strategies. A patient-derived xenograft (PDX) model is a valuable resource to solving the problem, provided that the model accurately reproduces the basic clinical and molecular genetic characteristics of a human tumor. Our purpose was to create a PDX model of a human tumor and to study 7 polymorphisms of the xenograft tissue and tissues of a donor tumor. Methods: PDX models of esophageal cancer were produced by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the BALB/c Nude athymic mice (n = 10 for one PDX generation). 5 PDX were generated. 7 polymorphisms (NFE2L2 (c.85G > A), NOTCH1 (c.1379C > T), NOTCH1 (c.1451G > T), ZNF750 (c.414C > A), ZNF750 (c.1621G > A), SMARCA4 (c.2272C > T), KMT2D (c.15508C > T)) were determined by the HRM analysis in tissues of each PDX generation and in the donor tumor. Results: All examined samples demonstrated the absence of ZNF750 (c.1621G > A) and NOTCH1 (c.1379C > T) polymorphisms and the presence of ZNF750 (c.414C > A), SMARCA4 (c.2272C > T) and KMT2D (c.15508C > T) polymorphisms. Polymorphisms in the NFE2L2 (c.85G > A) gene and in the NOTCH1 (c.1451G > T) gene were found in the F3, F4 and F5 PDX generations, but were absent in the donor tumor and the F1 and F2 generations. Conclusions: Molecular and genetic characteristics of the donor tumor change through several PDX generations. Early PDX generations are recommended for the studies as they better reproduce molecular and genetic characteristics of the original tumors.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Fanjuan Kong ◽  
Erdong Geng ◽  
Juan Ning ◽  
Zhiyu Liu ◽  
Aihua Wang ◽  
...  

Abstract Several papers studied dietary protein intake as a potential influence factor for esophageal cancer, but their findings were inconsistent. Thus, this meta-analysis was performed to identify the effect of protein intake on esophageal cancer risk. Potential case–control studies or cohort studies from the databases of Embase, Web of Science and PubMed were searched. The strength of association was quantified by pooling odds ratio (OR) and 95% confidence interval (CI). In total, 11 articles involving 2537 cases and 11432 participants were included in this meta-analysis. As a result, dietary protein intake had non-significant association on esophageal cancer risk overall (pooled OR = 1.11, 95% CI = 0.88–1.40). Meanwhile, we obtained consistent results in the subgroups analyses by study design, protein type, geographic locations and number of cases. Interestingly, dietary protein intake could significantly increase the risk of esophageal squamous cell carcinoma (pooled OR = 1.29, 95% CI = 1.02–1.62), instead of other disease type. To sum up, dietary protein intake had no significant association with esophageal cancer risk in the overall analysis; but, protein intake may be associated with the risk of esophageal squamous cell carcinoma. While some limitations existed in the present paper, more studies with large sample size are warranted to further confirm this result.


2021 ◽  
Author(s):  
Wenqiao Jia ◽  
Cong Wang ◽  
Ming Lu ◽  
Yufeng Cheng

Abstract Background:The effect of long term prediagnostic aspirin intake on the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. We aimed to reveal the effect of long term prediagnostic aspirin intake on survival of ESCC patients receiving radical surgery. Methods:147 eligible ESCC patients who received radical surgery for primary treatment were enrolled in this study. Patients who had used aspirin regularly for more than 3 months before diagnose were classified as aspirin group and patients who had never used aspirin before diagnose and surgery were served as non-aspirin group. The recurrence rate, disease-free survival (DFS) and overall survival (OS) were compared between the two groups to verify the effect of aspirin. Results:Patients were clarified into aspirin group (n=57) and non-aspirin group (n=90). The DFS and OS were both significantly shorter in aspirin group than non-aspirin group (DFS: 23.1±18.0 months vs. 30.9±19.8 months, P=0.018; OS: 29.8±17.4 months vs. 35.2±18.2 months, P=0.082). Survival analysis revealed that OS decreased in aspirin group than in non-aspirin group, however, it did not reach significance (P=0.074). DFS decreased significantly in aspirin group than non-aspirin group in both univariate (P=0.007) and multivariate (P=0.002) survival analysis. Subgroup analysis revealed that in pTNM stage 2, OS and DFS were reduced in non-aspirin group compared with aspirin group (P=0.048 and P=0.003, respectively), while no difference was found in stage 3.Conclusions:Long term prediagnostic aspirin intake may cause poor DFS in ESCC patients receiving radical surgery, especially for those in pTNM stage 2.


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