The functional consequences and prognostic value of dosage sensitivity in ovarian cancer

2017 ◽  
Vol 13 (2) ◽  
pp. 380-391 ◽  
Author(s):  
Zichuang Yan ◽  
Yongjing Liu ◽  
Yunzhen Wei ◽  
Ning Zhao ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Copy Number ◽  
Prognostic Value ◽  
Copy Number Alteration ◽  
Genetic Variations ◽  
Metastatic Spread ◽  
Important Class ◽  
Functional Consequences ◽  
Dosage Sensitivity

Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread.

EP970 PIK3R1mRNA expression is associated with copy number alteration in ovarian cancer

2019 ◽  
Author(s):  
IK Rzepecka ◽  
B Konopka ◽  
A Podgorska ◽  
A Stachurska ◽  
R Lotocka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Copy Number Alteration

scholarly journals 592 INPP4B gene is frequently deregulated via copy number alteration and underexpression in ovarian cancer

2021 ◽  
Author(s):  
IK Rzepecka ◽  
B Konopka ◽  
A Podgorska ◽  
R Lotocka ◽  
EM Cybulska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Copy Number Alteration

Outlier reset CUSUM for the exploration of copy number alteration data

2015 ◽  
Vol 14 (4) ◽  
Author(s):  
Yinglei Lai ◽  
Joseph L. Gastwirth
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Simulated Data ◽  
Threshold Value ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Data Set ◽  
Cusum Procedure ◽  
Truncated Normal

AbstractCopy number alteration (CNA) data have been collected to study disease related chromosomal amplifications and deletions. The CUSUM procedure and related plots have been used to explore CNA data. In practice, it is possible to observe outliers. Then, modifications of the CUSUM procedure may be required. An outlier reset modification of the CUSUM (ORCUSUM) procedure is developed in this paper. The threshold value for detecting outliers or significant CUSUMs can be derived using results for sums of independent truncated normal random variables. Bartel’s non-parametric test for autocorrelation is also introduced to the analysis of copy number variation data. Our simulation results indicate that the ORCUSUM procedure can still be used even in the situation where the degree of autocorrelation level is low. Furthermore, the results show the outlier’s impact on the traditional CUSUM’s performance and illustrate the advantage of the ORCUSUM’s outlier reset feature. Additionally, we discuss how the ORCUSUM can be applied to examine CNA data with a simulated data set. To illustrate the procedure, recently collected single nucleotide polymorphism (SNP) based CNA data from The Cancer Genome Atlas (TCGA) Research Network is analyzed. The method is applied to a data set collected in an ovarian cancer study. Three cytogenetic bands (cytobands) are considered to illustrate the method. The cytobands 11q13 and 9p21 have been shown to be related to ovarian cancer. They are presented as positive examples. The cytoband 3q22, which is less likely to be disease related, is presented as a negative example. These results illustrate the usefulness of the ORCUSUM procedure as an exploratory tool for the analysis of SNP based CNA data.

Distinct copy number alteration patterns as prognostic of endometrial cancer outcomes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5511-5511 ◽  
Author(s):  
Itai Max Pashtan ◽  
Donna S. Neuberg ◽  
Rameen Beroukhim ◽  
Helga B Salvesen ◽  
Andrew Cherniack
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Prognostic Value ◽  
Copy Number Alteration ◽  
Multivariable Analysis ◽  
Low Risk ◽  
Serous Carcinoma ◽  
Histologic Subtype ◽  
Therapeutic Decisions ◽  
Independent Population

5511 Background: Endometrial cancer is classified by tumor stage, histologic subtype and grade. However, a substantial proportion of presumed non-high risk cases recur, supporting the need for improved tools of prognostication. Methods: Using clinical and Affymetrix SNP 6.0 data from The Cancer Genome Atlas (TCGA) endometrial carcinoma project, we identified 4 somatic copy number alteration (SCNA) subtypes, established their prognostic value and validated them in an independent, population-based cohort from Norway. Patients had endometrioid, uterine papillary serous carcinoma (UPSC) or mixed histology tumors. Progression-free survival (PFS) was defined as time from diagnosis to recurrence or progression, and estimated by the Kaplan-Meier method. Results: Four groups of SCNA patterns were identified using hierarchical clustering: low SCNA, moderate SCNA, SCNA dominated by 1q amplification (1q amplified) and high SCNA level (serous-like). Their prognostic value was assessed in all TCGA patients (N = 292) and in a low risk subset with endometrioid histology, stage 1 disease (N = 210). In the full TCGA cohort, patients with low SCNA (reference group) had excellent 2-year PFS of 94%, while for moderate SCNA it was 84% (hazard ratio[HR] 2.7, p = .08). The 1q amplified and serous-like groups had significantly worse outcomes with 2-year PFS of 74% (HR 5.9, p= .002) and 74% (HR 6.0, p <.001), respectively. On multivariable analysis, adjusting for variables including stage and grade, 1q amplified and serous-like SCNA patterns remained independently prognostic (respectively, adjusted HR 6.2, p = .002 and 4.7, p = .02). Similar results were found in the low risk subset. The prognostic value of the SCNA patterns was validated in an independent group of patients with low risk disease (N = 57). 5-year PFS was 91% for low SCNA, 83% for moderate SCNA (HR 2.0, p = .58), 72% for 1q amplified (HR 3.7, p = .11) and 50% for the serous-like SCNA group (HR 6.7, p = .04). Conclusions: Four subtypes of DNA SCNA patterns in endometrial cancer were identified and validated to be prognostic of outcome. These novel biomarkers may be useful in guiding therapeutic decisions, and shed insight on the biology of more, or less, aggressive endometrial cancer.

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 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.

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