scholarly journals Increased expression of UBE2T predicting poor survival of ovarian cancer: based on bioinformatics analysis of UBE2s, clinical samples and the GEO database

2020 ◽  
Author(s):  
Ruoyao Zou ◽  
Haoya Xu ◽  
Feifei Li ◽  
Shengke Wang ◽  
Liancheng Zhu
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Gene Set Enrichment Analysis ◽  
Gene Copy ◽  
Serous Carcinoma ◽  
Benign Tumors ◽  
Mrna Levels ◽  
Geo Database

Abstract Background：Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive. Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited a strong correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A, UBE2B, UBE2C, UBE2G, UBE2R2 and UBE2T upregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, UBE2R2 and UBE2T upregulation and UBE2G downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P=0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer. Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

scholarly journals Increased Expression of UBE2T Predicting Poor Survival of Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples And the GEO Database

2020 ◽  
Author(s):  
Ruoyao Zou ◽  
Haoya Xu ◽  
Feifei Li ◽  
Shengke Wang ◽  
Liancheng Zhu
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Gene Set Enrichment Analysis ◽  
Gene Copy ◽  
Serous Carcinoma ◽  
Benign Tumors ◽  
Mrna Levels ◽  
Geo Database

Abstract Background：Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive. Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A, UBE2B, UBE2C, UBE2G, and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P=0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer. Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

scholarly journals Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

2020 ◽  
Author(s):  
Ruoyao Zou ◽  
Haoya Xu ◽  
Feifei Li ◽  
Shengke Wang ◽  
Liancheng Zhu
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Gene Set Enrichment Analysis ◽  
Gene Copy ◽  
Serous Carcinoma ◽  
Benign Tumors ◽  
Mrna Levels ◽  
Geo Database

Abstract Background： Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive.Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C , UBE2N , UBE2S , and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A , UBE2B , UBE2C , UBE2G , and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A , UBE2N , and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P= 0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer.Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

scholarly journals A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer

2021 ◽  
pp. 172460082199235
Author(s):  
Weina Zhang ◽  
Yu-min Zhang ◽  
Yuan Gao ◽  
Shengmiao Zhang ◽  
Weixin Chu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differential Diagnosis ◽  
Decision Tree ◽  
Copy Number ◽  
Malignant Tumors ◽  
Copy Number Variations ◽  
Ca 125 ◽  
Benign Tumors ◽  
Cell Free Dna ◽  
Free Dna

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors. Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled. Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy ( P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975. Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.

scholarly journals 4D Doppler Ultrasound in High Grade Serous Ovarian Cancer Vascularity Evaluation—Preliminary Study

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 582
Author(s):  
Marek Jerzy Kudla ◽  
Michal Zikan ◽  
Daniela Fischerova ◽  
Mateusz Stolecki ◽  
Juan Luis Alcazar
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Menopausal Status ◽  
Power Doppler ◽  
Serous Carcinoma ◽  
Benign Tumors ◽  
Control Group ◽  
High Grade ◽  
Tissue Samples ◽  
4D Ultrasound

The aim of the study was to evaluate the usefulness of 4D Power Doppler tissue evaluation to discriminate between normal ovaries and ovarian cancer tumors. This was a prospective observational study. Twenty-three cases of surgically confirmed ovarian High Grade Serous Carcinoma (HGSC) were analyzed. The control group consisted of 23 healthy patients, each matching their study-group counterpart age wise (±3 years) and according to their menopausal status. Transvaginal Doppler 4D ultrasound scans were done on every patient and analyzed with 3D/4D software. Two 4D indices—volumetric Systolic/Diastolic Index (vS/D) and volumetric Pulsatility Index (vPI)—were calculated. To keep results standardized and due to technical limitations, virtual 1cc spherical tissue samples taken from the part with highest vascularization as detected by bi-directional Power Doppler were analyzed for both groups of ovaries. Values of volumetric S/D indices and volumetric PI indices were statistically lower in ovarian malignant tumors compared to normal ovaries: 1.096 vs. 1.794 and 0.092 vs. 0.558, respectively (p < 0.001). The 4D bi-directional Power Doppler vascular indices were statistically different between malignant tumors and normal ovaries. These findings could support the rationale for future studies for assessing this technology to discriminate between malignant and benign tumors.

Expression of glucose-regulated protein 78 (GRP78) and its regulator microrna-181 during the development and progression of ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5579-5579
Author(s):  
Animesh Barua ◽  
Aparna Yellapa ◽  
Salvatore A Grasso ◽  
Jacques S Abramowicz ◽  
Sameer Sharma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Late Stage ◽  
Malignant Tumors ◽  
Early Stage ◽  
Distinct Pattern ◽  
Ovarian Tumors ◽  
Serous Carcinoma ◽  
Surface Epithelium ◽  
Benign Tumors ◽  
Potential Marker

5579 Background: Ovarian cancer (OVCA) is a lethal malignancy of women with a distinct pattern of metastasis through peritoneal dissemination. Sustained exposure of the ovaries to oxidative stress due to inflammatory processes including ovulatory genotoxicity, makes the ovarian microenvironment conducive to malignant cell proliferation. GRP78 is a stress-inducible protein which resides in the endoplasmic reticulum of the cell. Thus GRP78 may be a marker of ovarian tumor associated stress and could represent a therapeutic target for OVCA. The goal of this study was to examine if GRP78 expression increases in association with OVCA development and determine the molecular mechanism of its increase in ovarian tumors. Methods: All tissues were collected from patients who underwent surgery and processed for immunohistochemistry (IHC), proteomic study (2D-WB) and miRNA expression. Expression of GRP78 was examined in paraffin sections of normal ovaries (n = 20), benign (serous cystadenoma, n = 15 and cystadenofibroma, n = 5) and ovaries with papillary serous carcinoma at early stage (n= 20 at stages I and II) and late stage (n = 20, stages III and IV) by IHC and confirmed by 2D-WB (representative samples). Changes in miRNA-181 (post-translation regulator of GRP78) expression were examined by qRT-PCR. Results: GRP78 expression by normal ovarian surface epithelium and epithelium of benign tumors was very weak. In contrast, the intensity of GRP78 expression was significantly (p<0.05) high in early stage OVCA and increased further in late stage OVCA. An immunoreactive band of 78kDa detected by 2D-WB confirmed IHC observations. In contrast, expression of miRNA-181 by malignant tumors significantly (p<0.05) decreased as the tumor progressed to late stages. Conclusions: The results of the present study suggest that GRP78 expression is associated with the development and progression of malignant ovarian tumors. Increase in GRP78 expression was associated with the down-regulation of miRNA-181. Expression of GRP78 by malignant ovarian epithelium represents a potential marker with usefulness for targeted drug delivery. Support: Elmer and Sylvia Sramek Foundation.

scholarly journals Clinical Importance of Myc Family Oncogene Aberrations in Epithelial Ovarian Cancer

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
MoonSun Jung ◽  
Amanda J Russell ◽  
Catherine Kennedy ◽  
Andrew J Gifford ◽  
Kylie-Ann Mallitt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Mrna Expression ◽  
Clinical Significance ◽  
Copy Number ◽  
Family Members ◽  
Activity Score ◽  
Gene Copy ◽  
Myc Oncogene ◽  
Statistical Algorithm

Abstract Background The Myc oncogene family has been implicated in many human malignancies and is often associated with particularly aggressive disease, suggesting Myc as an attractive prognostic marker and therapeutic target. However, for epithelial ovarian cancer (EOC), there is little consensus on the incidence and clinical relevance of Myc aberrations. Here we comprehensively investigated alterations in gene copy number, expression, and activity for Myc and evaluated their clinical significance in EOC. Methods To address inconsistencies in the literature regarding the definition of copy number variations, we developed a novel approach using quantitative polymerase chain reaction (qPCR) coupled with a statistical algorithm to estimate objective thresholds for detecting Myc gain/amplification in large cohorts of serous (n = 150) and endometrioid (n = 80) EOC. MYC, MYCN, and MYCL1 mRNA expression and Myc activity score for each case were examined by qPCR. Kaplan–Meier and Cox-regression analyses were conducted to assess clinical significance of Myc aberrations. Results Using a large panel of cancer cell lines (n = 34), we validated the statistical algorithm for determining clear thresholds for Myc gain/amplification. MYC was the most predominantly amplified of the Myc oncogene family members, and high MYC mRNA expression levels were associated with amplification in EOC. However, there was no association between prognosis and increased copy number or gene expression of MYC/MYCN/MYCL1 or with a pan-Myc transcriptional activity score, in EOC, although MYC amplification was associated with late stage and high grade in endometrioid EOC. Conclusion A systematic and comprehensive analysis of Myc genes, transcripts, and activity levels using qPCR revealed that although such aberrations commonly occur in EOC, overall they have limited impact on outcome, suggesting that the biological relevance of Myc oncogene family members is limited to certain subsets of this disease.

Surface epithelial tumors of ovary - an analysis in a tertiary referral hospital

2013 ◽  
Vol 3 (5) ◽  
pp. 397-402 ◽  
Author(s):  
D Ghartimagar ◽  
A Ghosh ◽  
G KC ◽  
S Ranabhat ◽  
OP Talwar
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Data Bank ◽  
Serous Cystadenoma ◽  
Ovarian Tumors ◽  
Benign Tumors ◽  
Tertiary Referral ◽  
Tertiary Referral Hospital ◽  
Tertiary Referral Centre ◽  
Epithelial Tumors

Background: Ovarian cancer accounts for 3% of all cancers in females. About 80% of these are benign, and they occur mostly in young women between 20 and 45 years. Borderline tumors occur at slightly older ages while incidence of malignant tumors increases with age, occurring predominantly in perimenopausal and postmenopausal women. About 190,000 new cases and 114,000 deaths from ovarian cancer are estimated to occur annually worldwide. The aim of the study was to fi nd the incidence of surface ovarian tumor in a tertiary referral centre. Materials and methods: This was a retrospective study carried out in the department of pathology, Manipal Teaching Hospital from January 2001 to December 2012. Specimens were received from the same and other hospitals. Records were retrieved from the departmental data bank and were analyzed. Results: : A total of 310 cases of ovarian tumors have been reported in the same period. Among them, 180 cases were of surface epithelial origin and out of which 24 cases had bilateral tumors. Benign tumors comprised of 148 cases, 6 were borderline and 44 were malignant. Among these, the commonest was serous cystadenoma (98 cases) and the least common was malignant Brenner (2 cases). Combined or mixed tumor was seen in 9 cases. Conclusion: : In our study surface epithelial tumors comprised 58% of all ovarian tumors. In both benign and malignant cases, serous tumor was the commonest followed by mucinous tumors. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 397-402 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7868

scholarly journals Structure of the transcriptionally repressed phosphate-repressible acid phosphatase gene (PHO5) of Saccharomyces cerevisiae.

1986 ◽  
Vol 6 (1) ◽  
pp. 38-46 ◽  
Author(s):  
L W Bergman ◽  
M C Stranathan ◽  
L H Preis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Acid Phosphatase ◽  
Copy Number ◽  
Regulatory Control ◽  
Gene Copy ◽  
Growth Media ◽  
Regulatory Sequences ◽  
Mrna Levels ◽  
Acid Phosphatase Gene ◽  
Negative Supercoils

We developed a high-copy-number plasmid system containing the entire structural and regulatory sequences of the phosphate-repressible acid phosphatase (PHO5) gene and the TRP1/ARS1 replicator sequences of the yeast Saccharomyces cerevisiae to investigate the mechanism of repression-derepression of transcription. The resulting plasmid was used to transform either wild-type cells or a number of strains which contain mutations in various trans-acting regulatory loci for the production of acid phosphatase. Results of analysis of mRNA levels isolated from the transformed strains grown under repressed or derepressed conditions suggested that normal transcriptional regulation of the gene persisted, although gene copy number was significantly increased. Analysis of changes in linking number (i.e., the number of negative supercoils) of the plasmid isolated under repressed and derepressed growth conditions revealed that the transcriptionally inactive plasmid contained approximately three more negative supercoils than the transcriptionally active plasmid. This difference in topological state was similarly seen in a plasmid containing a sequence-related acid phosphatase gene (PHO11) under the same regulatory control system, but it was not seen in plasmids isolated from some strains containing mutations which caused either fully constitutive or nonderepressible production of acid phosphatase. Finally, analysis of the nucleosome positioning along the inactive gene sequence revealed that an abnormally broad internucleosomal spacer is present in a region presumed to function in the regulation of transcription by the level of Pi in the growth media.

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