Identification of a Multi-RNA-Type-Based Signature for Recurrence-Free Survival Prediction in Patients with Uterine Corpus Endometrial Carcinoma

2020 ◽  
Vol 39 (4) ◽  
pp. 615-630 ◽  
Author(s):  
Peizhi Wang ◽  
Zhi Zeng ◽  
Xiaoting Shen ◽  
Xiaohui Tian ◽  
Qingjian Ye
Keyword(s):  
Endometrial Carcinoma ◽  
Survival Prediction ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Uterine Corpus

scholarly journals Recurrence-associated gene signature optimizes recurrence-free survival prediction of colorectal cancer

2017 ◽  
Vol 11 (11) ◽  
pp. 1544-1560 ◽  
Author(s):  
Xianglong Tian ◽  
Xiaoqiang Zhu ◽  
Tingting Yan ◽  
Chenyang Yu ◽  
Chaoqin Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Signature ◽  
Survival Prediction ◽  
Recurrence Free Survival ◽  
Free Survival

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.

Tumor lymphocytic infiltration impacts recurrence in endometrioid-type endometrial carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15239-e15239
Author(s):  
Monica Avila ◽  
Bryan M. Fellman ◽  
Russell Broaddus
Keyword(s):  
Endometrial Carcinoma ◽  
Cox Regression ◽  
Predictive Biomarker ◽  
Lymphocytic Infiltration ◽  
Tumor Location ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Tumor Periphery ◽  
Endometrial Cancers ◽  
Endometrial Carcinomas

e15239 Background: Endometrial cancers that have mismatch repair deficiency are associated with higher numbers of tumor-associated lymphocytes, but the clinical significance of this observation is unknown. Our objective was to quantify CD3+ and CD8+ tumor lymphocytes of MMR intact (MMRi) and MMRd endometrioid-type endometrial carcinomas and determine if there was an association with survival. Methods: MMRd was defined as endometrial carcinomas with loss of MLH1 expression due to MLH1 gene methylation and determined by immunohistochemistry. MMRi was defined as positive expression of MLH1, MSH2, MSH6, and PMS2. This was followed by Aperio image-based quantification was used to assess CD3+ and CD8+ lymphocyte populations in different regions of the primary endometrial carcinomas, including tumor periphery (tumor-myometrial interface), tumor center (bounded on all sides by tumor), and tumor hotspot (area with highest number of lymphocytes). Recurrence-free survival was estimated using Kaplan Meier and Cox regression. Median follow up time was 44 months. Results: 180 patients with endometrial carcinoma were analyzed of which 132 were MMRi and 48MMRd. The MMRd group had significantly higher levels of CD3+ and CD8+ lymphocytes regardless of which tumor region was assessed (Figure 1a, P < 0.001). Lymphocyte counts in both MMRd and MMRi groups had wide standard deviations such that there was some overlap in counts between the groups (Figure 1). Both MMRd and higher CD3+ counts were associated with worse recurrence-free survival. CD3+ quantification in the tumor periphery captured 21/23 recurrences (Figure 1b, HR = 8.04; 95% CI: 1.88 -34.31; p = 0.005); this included all of the MMRd cases that recurred and 7 MMRi cases with higher numbers of CD3+ lymphocytes that also recurred. Conclusions: MMRd endometrial cancers have increased numbers of CD3+ lymphocytic infiltrates within the primary tumor. Higher CD3+ infiltration is associated with greater risk of recurrence regardless of tumor location. In predicting tumor recurrence, lymphocytic counts performed better than assessment of MMR. Thus, quantification of CD3+ lymphocytes should be explored as a predictive biomarker.

scholarly journals Ovarian preservation for premenopausal women with early-stage endometrial cancer: a Chinese retrospective study

2019 ◽  
Vol 47 (6) ◽  
pp. 2492-2498 ◽  
Author(s):  
Tianjiao Lyu ◽  
Lu Guo ◽  
Xiaojun Chen ◽  
Nan Jia ◽  
Chao Gu ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Recurrence Rate ◽  
Cox Regression ◽  
Premenopausal Women ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Ovarian Preservation ◽  
Significant Difference ◽  
Stage Ia

Objective This study aimed to retrospectively investigate the safety of ovarian preservation of premenopausal women with stage 1a endometrial carcinoma. Methods We performed a population-based study to identify surgically treated stage Ia endometrial cancer of premenopausal women who were diagnosed between August 1989 and December 2015 in our center. Survival outcomes and recurrence rate were examined for premenopausal women who underwent ovarian preservation. Recurrence-free survival rates were calculated following generation of Kaplan–Meier curves and were compared with the log-rank test. Cox regression analysis was performed to identify the independent factors affecting the recurrence rate. Results Patients with ovarian preservation tended to be significantly younger at diagnosis, have less myometrial invasion, and were less likely to undergo lymphadenectomy compared with women treated with bilateral salpingo-oophorectomy. There was no significant difference in recurrence-free survival between the two groups. In the Cox regression model, ovarian preservation remained an independent prognostic factor for improved overall survival. Conclusion Ovarian preservation does not have a negative effect on oncological outcomes. Ovarian preservation can be applied to premenopausal women with stage Ia endometrial carcinoma.

scholarly journals Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Cong Yu ◽  
Haining Qi ◽  
Yanhui Zhang ◽  
Wen Zhao ◽  
Guoying Wu
Keyword(s):  
Endometrial Carcinoma ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Clinicopathological Features ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Survival Prediction ◽  
Uterine Corpus ◽  
Gamma Glutamyl ◽  
Pathway Gene

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861–0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.

A 16‐mRNA signature optimizes recurrence‐free survival prediction of Stages II and III gastric cancer

2020 ◽  
Vol 235 (7-8) ◽  
pp. 5777-5786 ◽  
Author(s):  
Ke Peng ◽  
Erbao Chen ◽  
Wei Li ◽  
Xi Cheng ◽  
Yiyi Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Prediction ◽  
Recurrence Free Survival ◽  
Free Survival

Increased risk of recurrence in early-stage endometrial carcinoma after delays in adjuvant radiation treatment

2020 ◽  
Vol 31 (1) ◽  
pp. 73-77
Author(s):  
Simeng Zhu ◽  
Remonda Khalil ◽  
Osama Altairy ◽  
Charlotte Burmeister ◽  
Irina Dimitrova ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Endometrial Carcinoma ◽  
Radiation Treatment ◽  
Early Stage ◽  
Time Interval ◽  
Adjuvant Radiation ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Adjuvant Radiation Therapy ◽  
Disease Specific

ObjectiveThe benefits of adjuvant radiation treatment after hysterectomy have been confirmed in select patients with early-stage endometrial carcinoma. The goal of this study was to evaluate the prognostic impact of the time interval between hysterectomy and starting adjuvant radiation treatment in patients with early-stage endometrial carcinoma.MethodsOur database was searched for women with early-stage endometrioid endometrial cancer who received adjuvant radiation therapy after hysterectomy. The patients were classified into two groups based on the time interval to adjuvant radiation therapy (≤8 weeks or >8 weeks) after hysterectomy. Recurrence-free survival, disease-specific survival, and overall survival were compared between the two groups.ResultsFour hundred and sixty patients were identified. Median follow-up was 70.5 months (range 1–360). One hundred and seventy-six patients (38%) were 2009 International Federation of Gynecology and Obstetrics stage IA, 207 (45%) stage IB, and 77 (17%) stage II. Three hundred and fifty-four women (77%) received adjuvant radiation therapy within 8 weeks after hysterectomy. There was no statistically significant difference between the two groups in baseline demographics, disease and treatment characteristics, except for the modality of adjuvant radiation therapy. Patients who received adjuvant radiation therapy within 8 weeks experienced significantly less disease recurrence (9% vs 18%; p=0.01) and particularly less isolated vaginal recurrence (0% vs 6%, p=0.04). Five-year recurrence-free survival was 89% versus 80% (p=0.04), 5-year disease-specific survival was 93% for both groups, and 5-year overall survival was 86% versus 85% for patients who received adjuvant radiation therapy ≤8 and >8 weeks, respectively (p=0.88).ConclusionOur study suggests that delaying adjuvant radiation therapy beyond 8 weeks after hysterectomy is associated with significantly more cancer recurrences for women with early-stage endometrial carcinoma.

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