Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics

Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke

doi:10.1111/jog.12442

Cited by 95 publications

(88 citation statements)

References 80 publications

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“…Among these miRs, miR-126 typically employs a suppressive role in numerous types of cancer, including non-small cell lung cancer, cervical cancer, gastric cancer, colon cancer, clear-cell renal cell carcinoma and chronic myelogenous leukemia (6)(7)(8)(9)(10). Recently, miR-126 was suggested to function as a tumor suppressor in EC (1). However, the exact role of miR-126 in the mediation of EC cell migration and invasion has not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

“…The age-standardised incidence is 9.1 per 100,000 women per year in more developed countries, compared with 1.7 per 100,000 per year in less developed countries (3). The dysregulation of oncogenes and/or tumor suppressors has been demonstrated to serve a role in EC metastasis (1,4). Therefore, the development of potential molecular targets indicates promise for the treatment of EC progression.…”

Section: Introductionmentioning

confidence: 99%

“…Endometrial cancer (EC) is one of the most malignant tumors to threaten the health of women (1). Over the past decades, unremitting efforts to improve the diagnostics and subsequent treatment of EC have been attempted.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Zhao

Zhu

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRs) have been demonstrated to serve important roles in the development and progression of human cancer, primarily through the direct targeting of oncogenes or tumor suppressors. It has been previously suggested that miR-126 may be associated with endometrial cancer (EC). However, the exact role of miR-126 in the migration and invasion of EC cells has not yet been studied. The present study demonstrated that the expression of miR-126 was significantly decreased in EC tissues when compared with matched normal adjacent tissues. The current study reverse transcriptionquantitative polymerase chain reaction was performed in order to examine the expression level of miR-126. Wound healing and transwell assays were used to examine cell migration and invasion. A luciferase reporter assay was used to determine the targeting relationship and western blotting assay was performed to detect the protein expression. Furthermore, the overexpression of miR-126 significantly inhibited EC SKOV3 cell migration and invasion. Molecular mechanism investigation established that insulin receptor substrate 1 (IRS1) functioned as a direct miR-126 target, and its expression was negatively regulated by miR-126 at a post-transcriptional level in the SKOV3 cells. Additionally, the overexpression of IRS1 reversed the inhibitory effect of miR-126 overexpression on SKOV3 cell migration and invasion. In conclusion, the current study demonstrated that miR-126 inhibited EC cell migration and invasion, at least partially through the direct targeting of IRS1, suggesting that miR-126 may aid the treatment of EC metastasis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Zhao

Zhu

et al. 2015

Oncology Letters

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Section: Discussionmentioning

confidence: 99%

“…The most frequently mutated gene was PTEN with a mutation frequency of 47% of the endometrial carcinomas, where the literature shows a prevalence ranging from 26 to 82% [17, 20, 27-30]. PTEN mutations occur frequently in premalignant lesions and in type I endometrial cancer [27, 30, 31]. In our study, it was noted that PTEN mutations occurred only in endometrioid carcinomas and grade 2 tumours, which is similar to the existing literature [16, 27, 28].…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

et al. 2017

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Objective: To investigate whether next-generation sequencing (NGS) in ovarian and endometrial tumours can discover mutations with a relevant prognostic or predictive value. Methods: After a literature search, selected studies were critically appraised using the Quality in Prognostic Studies tool. Data on mutation incidence and correlations with prognostic and predictive items were extracted from relevant studies and compared to our own cohort consisting of 28 patients analysed using NGS. Results: Eight out of 739 articles were found eligible, including different tumour types. Prevalence of mutations in the KRAS gene ranged between 5.34 and 58.8% in ovarian cancer. Two studies showed a significant correlation between KRAS mutations and an improved disease free- and overall survival. Clinical data were available for 17 of our patients, mostly cases of endometrial carcinomas. KRAS, PIK3CA, CTNNB1, and TP53 were the most frequently mutated genes in endometrial carcinomas, and PTEN and CTNNB1 correlated with a higher FIGO stage. Conclusion: In the ovary KRAS mutation is associated with type I ovarian tumours (low-grade serous, mucinous, endometrioid, and clear-cell) and may seem to have a more favourable prognosis. The prognostic value of TP53 is still controversial. In endometrial tumours, PTEN shows a positive correlation with better prognosis. PIK3CA may have a correlation with poorer prognosis. CTNNB1 mutations in endometrial carcinomas could predict a worse prognosis.

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Establishment and validation of a prognostic nomogram based on a novel five‐DNA methylation signature for survival in endometrial cancer patients

Yin

Yuan

et al. 2020

Cancer Medicine

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Background This study aimed to explore the prognostic role of DNA methylation pattern in endometrial cancer (EC) patients. Methods Differentially methylated genes (DMGs) of EC patients with distinct survival from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylated genes as biomarkers for EC prognosis. The Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to construct a risk score model. A nomogram was built based on analysis combining the risk score model with clinicopathological signatures together, and then verified in the validation cohort and patients in our own center. Results In total, 157 DMGs were identified between different prognostic groups. Based on the LASSO analysis, five genes (GBP4, OR8K3, GABRA2, RIPPLY2, and TRBV5‐7) were screened for the establishment of risk score model. The model outperformed in prognostic accuracy at varying follow‐up times (AUC for 3 years: 0.824, 5 years: 0.926, and 7 years: 0.853). Multivariate analysis identified four independent risk factors including menopausal status (HR = 3.006, 95%CI: 1.062–8.511, p = 0.038), recurrence (HR = 2.116, 95%CI: 1.061–4.379, p = 0.046), lymph node metastasis (LNM, HR = 3.465, 95%CI: 1.225–9.807, p = 0.019), and five‐DNA methylation risk model (HR = 3.654, 95%CI: 1.458–9.161, p = 0.006) in training cohort. The performance of the nomogram was good in the training (AUC = 0.828), validation (AUC = 0.866) and the whole cohorts (AUC = 0.843). Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan–Meier survival curve also proved to be significantly different ( p < 0.01). The subgroup analysis in different stratifications indicated that the accuracy was high in different subgroups for age, histological type, tumor grade, and clinical stage (all p < 0.01). Conclusions Briefly, our work established and verified a five‐DNA methylation risk model, and a nomogram merging the model with clinicopathological characteristics to facilitate individual prediction of EC patients for clinicians.

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Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics

Cited by 95 publications

References 80 publications

MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

Establishment and validation of a prognostic nomogram based on a novel five‐DNA methylation signature for survival in endometrial cancer patients

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