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

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.

Download Full-text

LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer

Frontiers in Oncology ◽

10.3389/fonc.2016.00190 ◽

2016 ◽

Vol 6 ◽

Cited By ~ 2

Author(s):

Ivo Noci ◽

Flavia Sorbi ◽

Luca Mannini ◽

Elisabetta Projetto ◽

Serena Pillozzi ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Value ◽

Low Risk ◽

Receptor Expression ◽

Hcg Receptor

Download Full-text

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Uterine Serous Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000264 ◽

2014 ◽

Vol 24 (Supp 3) ◽

pp. S83-S89 ◽

Cited By ~ 32

Author(s):

Satoru Sagae ◽

Nobuyuki Susumu ◽

Akila N. Viswanathan ◽

Daisuke Aoki ◽

Floor J. Backes ◽

...

Keyword(s):

Endometrial Cancer ◽

Gynecologic Cancer ◽

Survival Rates ◽

Serous Carcinoma ◽

Molecular Characteristics ◽

Histologic Subtype ◽

High Propensity ◽

Stage Disease ◽

Uterine Serous Carcinoma

ObjectivesUterine serous carcinoma (USC) represents a rare and aggressive histologic subtype of endometrial cancer, associated with a poor prognosis. This article critically reviews the literature pertinent to the epidemiology, pathology, molecular biology, diagnosis, management, and perspectives of patients with USC.MethodsAs one of a series of The Gynecologic Cancer InterGroup (GCIG) Rare Tumor Working Group in London, November 2013, we discussed about USC many times with various experts among international GCIG groups.ResultsBoth USC and approximately 25% of high-grade endometrioid tumors represent extensive copy number alterations, few DNA methylation changes, low estrogen and progesterone levels, and frequent P53mutations. Uterine serous carcinoma shares molecular characteristics with ovarian serous and basal-like breast carcinomas. In addition to optimal surgery, platinum- and taxane-based chemotherapy should be considered in the treatment of both early- and advanced-stage disease. The combination of radiation and chemotherapy appears to be associated with the highest survival rates. The role of radiation therapy in the management of this disease, with a high propensity for distant failures, remains elusive.ConclusionsUterine serous carcinoma is a unique and biologically aggressive subtype of endometrial cancer and should be studied as a distinct entity. Futures studies should identify the optimized chemotherapy and radiation regimens, sequence of therapy and schedule, and the role of targeted biologic therapy.

Download Full-text

Prognostic value of 18F-FDG PET/CT for identifying high- and low-risk endometrial cancer patients

Ginekologia Polska ◽

10.5603/gp.2016.0032 ◽

2016 ◽

Vol 87 (7) ◽

pp. 493-497 ◽

Cited By ~ 5

Author(s):

Emre Özgü ◽

Murat Öz ◽

Yunus Yıldız ◽

Burçin Salman Özgü ◽

Salim Erkaya ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Patients ◽

Fdg Pet ◽

Prognostic Value ◽

Low Risk ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Download Full-text

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

10.21203/rs.3.rs-41533/v1 ◽

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.

Download Full-text

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

10.21203/rs.3.rs-41533/v2 ◽

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.

Download Full-text

Somatic copy number alteration burden and TP53 status drive radio-resistance in endometrial cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.05.333 ◽

2020 ◽

Vol 159 ◽

pp. 206-207

Author(s):

R. Vargas ◽

A. Petty ◽

M. Kuznicki ◽

T. Bera ◽

P. Gopal ◽

...

Keyword(s):

Endometrial Cancer ◽

Copy Number ◽

Copy Number Alteration ◽

Tp53 Status ◽

Somatic Copy Number Alteration

Download Full-text

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

Molecular BioSystems ◽

10.1039/c6mb00625f ◽

2017 ◽

Vol 13 (2) ◽

pp. 380-391 ◽

Cited By ~ 6

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.

Download Full-text

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

10.21203/rs.3.rs-35103/v1 ◽

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.

Download Full-text

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment

Frontiers in Oncology ◽

10.3389/fonc.2021.612450 ◽

2021 ◽

Vol 11 ◽

Author(s):

Camilla Nero ◽

Francesca Ciccarone ◽

Antonella Pietragalla ◽

Simona Duranti ◽

Gennaro Daniele ◽

...

Keyword(s):

Risk Assessment ◽

Endometrial Cancer ◽

Adjuvant Therapy ◽

Copy Number ◽

Early Stage ◽

Tumor Grade ◽

Risk Groups ◽

Molecular Classification ◽

The Cancer Genome Atlas ◽

Histologic Subtype

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient’s risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Download Full-text