- Overexpression of UBE2C in esophageal squamous cell carcinoma tissues and molecular analysis. - 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). - 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 p <. - 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.. - However, few studies have considered a potential role for gene regulation of UBE2C in ESCC.. - In this study, we first performed in-house RNA-seq to determine the expression of UBE2C in ESCC tissues.. - Finally, we mined the public databases and conduct a comprehensive analysis of UBE2C expression based on in-house RNA-seq, in- house IHC and public databases. - An in silico method was used to predict the upstream miRNAs and lncRNAs of UBE2C to elucidate the molecular mech- anism of UBE2C in ESCC. - The search keywords were “Esophageal cancer.” The fol- lowing were the inclusion criteria: the expression data (including the related mRNA, miRNA, or lncRNA) and their annotation information from RNA-seq and tissue microarrays must be available. - The mRNA expression of UBE2C in ESCC cell lines. - Copy number analysis of UBE2C. - The copy number variation of UBE2C was then automatically analyzed and the results were displayed directly on the web page.. - We used 12 miRNA prediction tools (miRWalk, miRanda, miRDB, miRNAMap, PITA, RNAhybrid, Microt4, mirbridge, miRMap, Pictar2, RNA22, Targetscan) to predict up- stream miRNAs of UBE2C. - in ESCC as candidate lncRNAs. - We used the receiver operating charac- teristic curve (ROC) and the area under the curve (AUC) to assess the ability of UBE2C to distinguish ESCC from non-cancerous tissue. - 2 Violin plot of UBE2C mRNA and protein overexpression in ESCC tissues assessed by in-house RNA-seq, in-house IHC, TCGA-GTEx RNA-seq and tissue microarray. - a, Violin plot of UBE2C mRNA based on in-house RNA-seq. - b, Violin plot of UBE2C protein based on in-house IHC. - c, Violin plot of UBE2C mRNA based on TCGA-GTEx RNA-seq. - d-I, Violin plot of UBE2C mRNA based on tissue microarray. - 0 indicated upregulation of UBE2C, candidate miRNAs and candidate lncRNAs expression in ESCC compared with that in non-cancerous tissue. - We integrated all the data to draw the sROC curve for further clarification of the clinical diagnostic value of UBE2C for ESCC. - The prognostic value of UBE2C in ESCC was analyzed using the Kaplan-Meier (KM)-plotter database. - The average expression value of UBE2C mRNA was sig- nificantly higher in ESCC than in control p <. - 3 ROC curves of UBE2C mRNA and protein overexpression in ESCC tissues assessed by in-house RNA-seq, in-house IHC, TCGA-GTEx RNA-seq and tissue microarrays. - a, ROC curve of UBE2C mRNA based on in-house RNA-seq. - b, ROC curve of UBE2C protein based on in-house IHC. - c, ROC curve of UBE2C mRNA based on TCGA-GTEx RNA-seq. - d-I, ROC curve of UBE2C mRNA based on tissue microarrays. - UBE2C protein was overexpressed in ESCC tissues. - The expression of UBE2C protein in ESCC and the rela- tionship between UBE2C protein and UBE2C mRNA overexpression were analyzed by immunohistochemistry of 162 ESCC tissues and adjacent tissues. - Among 144 cases of ESCC tissue showed positive expression of UBE2C protein (with a specified score of more than 6 being positive, and a score of less than or equal to 6 be- ing negative), whereas only 47 (33%) of 142 adjacent tis- sues showed positive expression of UBE2C (p <. - 3b), indicating that UBE2C protein and mRNA were highly expressed in ESCC tissues.. - UBE2C mRNA was overexpressed in ESCC tissues in public data. - The average expression value of UBE2C was sig- nificantly higher in ESCC tissues than in the control tissues p <. - The expres- sion relationship of UBE2C in cancer tissues and control tissues was demonstrated by drawing violin diagrams and ROC curves. - The average expression of UBE2C indicated significantly overexpression in ESCC tissues compared to. - 4 UBE2C protein overexpression in ESCC tissues assessed by in-house IHC. - 3d-i), suggesting significant differences in the expression of UBE2C in the ESCC versus the control group, and that the cancer tissues showed significantly high expression.. - Comprehensive analysis confirmed the UBE2C is overexpressed in ESCC. - UBE2C was highly expressed in ESCC after comprehensive analysis) (data showed in supplementary information).. - We further examined the mRNA expression level of UBE2C by combining the large throughput data from the public data with our in-house RNA-seq data (a total of 628 cancer tissues and 1695 healthy control tissues).. - The SMD of UBE2C mRNA expression values was 2.13 (95%CI p <. - Therefore, in ESCC tissues, UBE2C mRNA was in a significantly upregulated state. - 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- house IHC, TCGA-GTEx RNA-seq and tissue micro- array), including 772 ESCC samples and 1837 control samples, to calculate a combined SMD and sROC. - 5a), which indicated significant overexpres- sion of UBE2C in ESCC tissues. - The 27 esophageal cancer cell lines screened from CCLE (https://portals.broadinstitute.org/ccle) for further ana- lysis of mRNA expression of UBE2C in ESCC all showed UBE2C expression (Fig. - Correlation between UBE2C expression and the clinical characteristics in ESCC. - Results of survival analysis showed that ESCC patients with high expression of UBE2C tended to have higher overall survival (OS), and p value was not statistically significant (Fig. - Interestingly, through subgroup ana- lysis of ESCC patients at different stages, we found that in early stage of ESCC patients (stage II), patients with high expression of UBE2C tended to have higher OS, and p value was not statistically significant (Fig. - However, in advanced stage of ESCC (stage III), patients with high expression of UBE2C had a lower five-year survival rate, and p value was not statistically significant (Fig. - In addition, by analyzing the relapse-free survival (RFS) of UBE2C in the ESCC dataset, we found that ESCC patients with high expression of UBE2C tended to have a lower risk of recurrence, and the p value was not statistically significant (Fig. - The copy number analysis of UBE2C in the esophageal cancer dataset showed that UBE2C was amplified in 32 (6%) of 559 cases (Fig. - The mechanism of UBE2C in ESCC was further ana- lyzed by selecting 4976 genes significantly differentially expressed in ESCC and 1632 genes significantly related with UBE2C by RRA combined with artificial ranking.. - The potential miRNAs upstream of UBE2C were explored using a variety of miRNA online databases (miRWalk, miRanda, miRDB, miRNAMap, PITA, RNA- hybrid, Microt4, mirbridge, miRMap, Pictar2, RNA22,. - 5 The comprehensive UBE2C expression level in ESCC and ESCC cell lines. - a, Forest plot of UBE2C mRNA expression in ESCC based on in- house RNA-seq, in-house IHC, TCGA-GTEx RNA-seq and tissue microarrays. - b, sROC of UBE2C in ESCC tissues based on in-house RNA-seq, in-house IHC, TCGA-GTEx RNA-seq and tissue microarrays. - The possible targeting relationship among lncRNA, miRNA, and UBE2C in ESCC tumor tissue was further clarified by calculating the combined SMD of the candidate miRNA and lncRNA expression values. - The pooled SMD of lncRNA HCP5 in ESCC was 1.32 (95%CI p <. - 10a), indicating that lncRNA HCP5 was highly expressed in ESCC. - The pooled SMD of miRNA hsa-miR-139-5p in ESCC tissue was CI. - 10b), indicating that miRNA hsa-miR-139-5p was downregulated in ESCC tissues.. - 6 Kaplan-Meier survival analysis of UBE2C in ESCC based on Kaplan Meier-plotter databases. - a, OS survival analysis of UBE2C in ESCC in all stage. - b, OS survival analysis of UBE2C in ESCC in stage II. - c, OS survival analysis of UBE2C in ESCC in stage III. - d, RFS survival analysis of UBE2C in ESCC in all stage. - e, RFS survival analysis of UBE2C in ESCC in stage II. - Moreover, the UBE2C and hsa-miR-139-5p analysis based on in-house RNA-seq showed that the average expression value of UBE2C mRNA was signifi- cantly higher in ESCC than in control p <. - expression value of hsa-miR-139-5p miRNA was signifi- cantly lower in ESCC than in control p <. - with the correlation results of UBE2C and hsa-miR- 139-5p in TCGA (Pearson r. - Our analysis of the expression of UBE2C in 772 ESCC tissue samples and 1837 non-cancerous tissue control samples, which is the largest sample size analyzed to date, confirmed a significantly high expression of UBE2C in ESCC tissue. - Together with our GO and KEGG analysis of UBE2C related genes and ESCC differential genes, we were able to construct a ceRNA network related to UBE2C in ESCC. - Based on our findings, we speculate that this ceRNA axis consisting of HCP5/hsa-miR-139- 5p/UBE2C may exist in ESCC. - The expression level of UBE2C has also been related to the aggressiveness of the tumor [3]. - b, the related protein of UBE2C in PPI network. - d, Copy number variation of UBE2C based on esophageal cancer. - research on UBE2C in ESCC has not been sufficiently comprehensive.. - The integration of large numbers of sample data in the present study confirmed the high expression of UBE2C in ESCC, as well as a significant correlation between ex- pression and gender (The expression level of UBE2C was significantly higher in males than in females). - Inter- estingly, several studies have verified the expression level of UBE2C in ESCC through various detection methods.. - demonstrated an upregu- lated expression of UBE2C mRNA and protein in ESCC tissues through qRT-PCR and immunohistochemical analysis of ESCC and control tissue specimens and fur- ther confirmed, with in vitro experiments, that UBE2C. - proposed that the expression of UBE2C in ESCC may be regulated by transcription factor FOXM1 and that upregulation of UBE2C may affect the occurrence of tumors by acting on cell cycle pathways, a common phenomenon in human tumors [20]. - In addition, through the survival analysis of UBE2C in the ESCC dataset, we found that UBE2C is likely to play different roles in different stages of the ESCC. - 10 Forest plot of HCP5 and hsa-miR-139-5p expression and correlation among HCP5, hsa-miR-139-5p and UBE2C in ESCC based on included microarray. - a, Forest plot of HCP5 expression in ESCC based on included microarray. - b, Forest plot of hsa-miR-139-5p expression in ESCC based on included microarray. - 11 a, Box plot of UBE2C mRNA expression based on in-house RNA-seq. - copy number amplification of UBE2C gene was ob- served, although no correlation between amplification and prognosis was found. - Several studies have confirmed the significantly high expression of UBE2C in ESCC, but the role of UBE2C in ESCC has not yet been determined. - findings of the present study now indicate an involve- ment of ceRNA in ESCC as well.. - Interestingly, Shuo has also confirmed in his doctoral thesis that the expression of has-miR-139-5p was downregulated in ESCC tissues. - We speculate that a HCP5/has- miR-139-5p/UBE2C axis may also exist in ESCC.. - One is that the researchers who conducted the included studies did not agree on the location of UBE2C expression or on the evaluation, test methods, and defined values of positive and negative, which may affect the accuracy of our results. - therefore, expression of UBE2C in the body fluids of ESCC patients and non-ESCC healthy people needs to be further stud- ied. - In summary, this study indicates that UBE2C is overex- pressed in ESCC tissues and that the high expression of UBE2C may influence the biological function of ESCC by regulating the cell cycle. - UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines. - clinicopathological significance of UBE2C in breast cancer: a study based on immunohistochemistry, microarray and RNA-sequencing data
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