High-intermediate risk endometrial cancer: Can gene expression predict recurrence?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5591-5591 ◽  
Author(s):  
Cindy Tawfik ◽  
Beomjy Kim ◽  
Angelina Londono ◽  
Ashwini A. Katre ◽  
Deborah L Della Manna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Adjuvant Treatment ◽  
Treatment Strategies ◽  
Gene Expression Signature ◽  
Progression Free Survival ◽  
Intermediate Risk ◽  
Recurrent Tumor ◽  
Original Tumor ◽  
Advanced Analysis

5591 Background: Studies have shown that adjuvant therapy increases progression free survival, but does not affect overall survival in patients with high-intermediate risk (H-IR) endometrial cancer (EMCA). Our objective was to develop a gene expression signature that may help identify H-IR EMCA patients with the highest risk of recurrence to help guide treatment strategies. Methods: Data was collected on all patients that met H-IR EMCA criteria diagnosed between 2000-2010 at UAB (n = 292). Of the patients that did not receive adjuvant treatment, 13 patients that recurred were matched to 13 patients that did not recur and original tumor was compared. Of those that recurred, 5 patients had original and recurrent tumor available for analysis. Gene expression data was collected using the Nanostring nCounter PanCancer Pathway 770 gene panel. Data was analyzed using nSolver Advanced Analysis Software. A fold change (FC) of ≥ ± 2 (p < 0.05) was used to identify genes with a significant expression difference. Results: Comparing the 13 patients that recurred to the 13 that did not, there were 5 genes with FC ≥ +2: BAIAP3, PLCB1, IL1R1, NOS3 and RAD50. There were 29 genes with FC ≥ -2; the top 3 genes with decreased expression (FC ≥ -10) were: BMP7, FGF18, WNT7A. Genes in the Cell Cycle (CC) pathway were significantly different in the patients that recurred (p = 0.02). There were 61 genes with FC ≥ +2 when comparing the original tumor to recurrent tumor; the top 3 genes with increased expression (FC ≥ 10) were: FGF18, CCND1, HIST1H3H (p < 0.05). There were 50 genes with FC ≥ -2; the top 3 genes with decreased expression (FC ≥ -1000) were: HOXA11, LEFTY2 and SFRP4. Wnt, Hedgehog, Chromatin Modification, DNA repair, TGF-β, MAPK, and CC pathways were significantly different in the recurrent samples compared to the original tumor (p < 0.05). Conclusions: Our data suggests that gene expression panels could better identify patients that warrant adjuvant treatment. The CC pathway, which is significantly different in the original tumor from those that recurred and those that did not, was further altered in the recurrent tumor samples. Additional studies are on-going to validate these findings and to further investigate DNA mutation differences in larger cohort of patients.

scholarly journals A gene expression signature for defining aggressive phenotype and prognosis in intermediate-risk acute myeloid leukemia

2016 ◽  
Author(s):  
Ailing Deng
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Gene Expression Analysis ◽  
Gene Expression Signature ◽  
Intermediate Risk ◽  
Multivariable Model ◽  
Differential Gene Expression Analysis ◽  
Molecular Pattern ◽  
Differential Gene ◽  
Differential Genes

Intermediate-risk AML is a group of heterogeneous disease, complete and accurate understanding of their molecular pattern are urgent. We downloaded gene expression profile from TCGA, and performed the differential gene expression analysis of 98 intermediate-risk AML patients according to the different clinical outcome. By studying the overlap of differential genes based on OS and EFS classification, we identified 6 distinct genes (SPANXC, ADAMTS15, C8B, FAM183A, FLJ42875 and PXDN). Only FLJ42875 and PXDN were relatively widely expressed in intermediate-risk AML. Moreover, Q1 (0-25%) of PXDN was associated significantly shortened OS and EFS (P=0.0001, P=0.0032, respectively), while OS and EFS of Q2 (25-50%) of FLJ42875 expression group were significantly longer than that of low FLJ42875 expression patients (P=0.0157, P=0.0074, respectively). In the multivariable model of OS, PXDN Q1 group had a shorter OS and EFS (P < 0.001, P =0.009; respectively). While FLJ42875 Q2 group had a tendency of prolonged OS and EFS (P=0.050, P=0.023; respectively). Our results suggest that FLJ42875 and PXDN may play a role in the leukemogenesis of intermediate-risk AML.

The impact of adjuvant treatment in intermediate risk, Stage I endometrial cancer with somatic CTNNB1 mutation

2019 ◽  
Vol 153 (3) ◽  
pp. e8
Author(s):  
K.C. Kurnit ◽  
B. Fellman ◽  
S.S. Xie ◽  
J. Bowser ◽  
G.B. Mills ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Treatment ◽  
Stage I ◽  
Intermediate Risk ◽  
The Impact ◽  
Ctnnb1 Mutation

scholarly journals RNF183 Is a Prognostic Biomarker and Correlates With Tumor Purity, Immune Infiltrates in Uterine Corpus Endometrial Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Rong Geng ◽  
Yuhua Zheng ◽  
Lijie Zhao ◽  
Xiaobin Huang ◽  
Rong Qiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Progression Free Survival ◽  
M2 Macrophage ◽  
Free Survival ◽  
Uterine Corpus ◽  
Immune Infiltration ◽  
Tumor Purity ◽  
High Level

RNF183, a member of the E3 ubiquitin ligase, has been shown to involve in carcinogenesis and proposed as one of the biomarkers in Uterine Corpus Endometrial Carcinoma (UCEC). However, no research focused on the role of RNF183 in UCEC. We analyzed the expression and immune infiltration of RNF183 in UCEC. TIMER, UALCAN, and GEPIA were used to analyze the gene expression of RNF183. We emplored Kaplan-Meier Plotter to examine the overall survival and progression-free survival of RNF183, and applied GeneMANIA to identify RNF183-related functional networks. LinkedOmics was helpful to identify the differential gene expression of RNF183, and to further analyze gene ontology and the genome pathways in the Kyoto Protocol. Finally, we used TIMER to investigate the immune infiltration of RNF183 in UCEC. Otherwise, we partly verified the results of bioinformatics analysis that RNF183 controlled ERα expression in ERα-positive Ishikawa cells dependent on its RING finger domain. We also found that ERα increased the stability of RNF183 through the post-translational mechanism. Together, patients with a high level of RNF183 harbor favorable overall and progression-free survival. High expression of RNF183 was associated with a low stage, endometrioid, and TP53 Non-Mutant status in endometrial cancer. The RNF183 expression was greater at higher expression and the tumor stage was greater at the lower level. On the side of immunization, high level of RNF183 in UCEC is negatively related to tumor purity, infiltrating levels of CD4 + T cells, neutrophils, and dendritic cells. Besides, the expression of RNF183 in UCEC is significantly correlated with the expression of several immune cell markers, including B cell, M1 macrophage marker, M2 Macrophage, Dendritic cell, Th1 markers, Th2 markers, Treg markers, and T cell exhaustion markers, indicating its role in regulating tumor immunity. These results suggested that RNF183 may be considered as a novel prognostic factor in endometrial cancer and an early diagnostic indicator for patients with UCEC.

scholarly journals Increased angiogenesis is associated with a 32-gene expression signature and 6p21 amplification in aggressive endometrial cancer

Oncotarget ◽  
2015 ◽  
Vol 6 (12) ◽  
pp. 10634-10645 ◽  
Author(s):  
Ingunn M. Stefansson ◽  
Maria Raeder ◽  
Elisabeth Wik ◽  
Monica Mannelqvist ◽  
Kanthida Kusonmano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Gene Expression Signature ◽  
Expression Signature

Patterns of Adjuvant Therapy for Endometrial Cancer: Single Institutional Experience in Thailand

2015 ◽  
Vol 25 (4) ◽  
pp. 665-672 ◽  
Author(s):  
Siriwan Tangjitgamol ◽  
Jakkapan Khunnarong ◽  
Kanyarat Katanyoo ◽  
Sunamchok Srijaipracharoen ◽  
Thaovalai Thavaramara ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Tumor Grade ◽  
Poor Performance Status

AimThe aim of this study was to evaluate the use of adjuvant therapy and treatment outcomes in patients with endometrial cancer (EMC).MethodsPatients with EMC treated in the institution were identified. Data collected were age, stage of disease, histopathology, and adjuvant therapy. Progression-free survival (PFS) and overall survival (OS) were studied.ResultsThe median age of 383 patients was 57 years (30–86 years). Majority had early-stage diseases (76.5%), endometrioid histopathology (87.2%), and high-grade tumors (74.9%). Less than half (44.4%) had adjuvant therapy. Pelvic radiation was the most common type of adjuvant treatment. We found that 25.7% of stages III to IV patients did not have adjuvant therapy (mainly from old age or poor performance status). On the other hand, 21.5% of patients with stage IA had adjuvant treatment (owing to risk factors or other synchronous cancers). The 5-year PFS and 5-year OS (95% confidence interval) were 84.3% (80.5%–88.1%) and 81.2% (77.1%–85.4%), respectively. Significant prognostic factors for survival by univariable analyses were stage, tumor grade, and histopathology. By multivariable analyses, significant prognostic factors were stage, tumor grade (only for OS), histopathology, and adjuvant therapy. Focusing on stage and adjuvant therapy, we found that the PFS and OS of early-stage patients who had or did not have adjuvant therapy were not significantly different, whereas the PFS and OS of advanced-stage patients who had adjuvant treatment were significantly higher than the PFS and OS of those who did not have adjuvant treatment.ConclusionsThe use of adjuvant therapy for patients with EMC was not according to the standard recommendation in all patients for many reasons. The benefit of adjuvant therapy was demonstrated in advanced- but not in early-stage cancer.

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