Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique.

To evaluate the role of serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels for predicting and monitoring the recurrence of endometrial endometrioid carcinoma (EEC) and assessing preoperative risk stratification in EEC patients. A total of 434 EEC patients were selected for this retrospective study between May 2011 and August 2018. Serum HE4 and CA125 levels were analyzed before the initial treatment, at the first postoperative follow-up, and at recurrence or the last follow-up. Patients were risk stratified according to the European Society for Medical Oncology (ESMO), European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guideline. We compared the ability of these biomarkers for prediction and monitoring by performing receiver operating characteristic curve analysis and identified optimal cut-off values by determining the Youden index. Kaplan-Meier analyses were also performed to determine prognostic value. Preoperative serum HE4 was identified as a significant predictor for the recurrence of EEC (p = 0.014). Preoperative serum HE4 and CA125 levels were related to depth of myometrial invasion, lymph node status and FIGO stage. Serum HE4 and CA125 levels were both statistically significant markers for monitoring the recurrence of EEC (P = 0.000 for each biomarker). When combined, the two markers showed higher levels of sensitivity and specificity. The two biomarkers were also significant biomarkers for evaluating the risk stratification of patients undergoing lymphadenectomy (P = 0.000 for each biomarker). For premenopausal stage I patients, preoperative serum HE4 and CA125 levels were significant predictors of the need for ovarian preservation (P = 0.000 and P = 0.002, respectively). For premenopausal patients with stage I intramucosal differentiation, preoperative serum levels of HE4 were significant predictors for fertility preservation (P = 0.024). Preoperative serum HE4 level can be used to predict the recurrence of EEC. Postoperative serum HE4 and CA125 levels can be used to monitor the recurrence of EEC and are more sensitive when combined. Preoperative serum levels of CA125 and HE4 levels are of significant value for risk stratification in EEC patients.

The incidence of endometrial endometrioid carcinoma (EEC) has been gradually increasing over the past decade. Fertility-sparing therapy with progestin is a treatment option for EEC or endometrial atypical hyperplasia (AH). The present study evaluated the role of numerous prognostic factors following fertility-sparing therapy for EEC or AH. Furthermore, the present study assessed the strength of various clinicopathological indicators for the prediction of treatment efficacy. A retrospective analysis was performed of patients with EEC and AH who received fertility-sparing therapy between August 2013 and September 2021 at Peking University People\'s Hospital (Beijing, China). Endometrial specimens were obtained from each patient after 3 months of treatment and at the end of the fertility-sparing therapy, before treatment efficacy and prognosis were evaluated using the χ2 test. Furthermore, the protein expression levels of EEC biomarkers, such as estrogen receptor (ER), progesterone receptor (PR), paired box 2 (PAX2), PTEN and p53 were assessed using immunohistochemistry. The overall complete response (CR) rate of fertility-sparing treatment in the EEC group was 67.39% (31/46), whereas that in the AH group was 86.49% (32/37). The difference between the CR rates in the EEC and AH groups was statistically significant (P<0.05). There was no association between prognosis after treatment and ER, PAX2, PTEN or Ki-67 expression in the initially untreated AH or EEC groups. However, tissues with >50% positive PR expression were demonstrated to have a higher CR rate compared with those with ≤50% positive PR expression in both the EEC and AH groups. Furthermore, the PAX2-positive group tended to demonstrate higher CR rates compared with the PAX2-negative group in the patients with EEC. In conclusion, these data suggested that fertility-sparing therapy is effective for patients with EEC and AH who wish to remain fertile after treatment. Specifically, in the AH group, a higher proportion of patients achieved a CR whilst also achieving this more rapidly. Furthermore, PR was demonstrated to be a useful marker for the evaluation of EEC and AH.

Endometrial carcinoma (EC) is one of the most common types of gynecological cancer. Long noncoding RNAs (lncRNAs) are associated with the carcinogenesis and progression of EC. In the following review, the emerging role of lncRNAs in EC initiation and progression is considered. The profile of lncRNAs is becoming higher as the contribution of lncRNAs to carcinogenesis through diverse mechanisms is being increasingly recognized, including in EC. A number of lncRNA-profiling studies have identified aberrantly expressed lncRNAs in EC tissue, and the regulatory network associated with these lncRNAs may be critical in EC progression. Additionally, certain lncRNAs may have diagnostic and/or prognostic significance. The potential function of lncRNAs as prospective therapeutic and prognostic targets in EC will be evaluated.

Endometrial cancer is the most common gynecologic malignancy, about 80% of which is endometrial endometrioid carcinoma. Dysregulation of spindle assembly checkpoint plays a vital role in endometrial endometrioid carcinoma tumorigenesis and progression. The purpose of this study was to explore how tyrosine threonine kinase, a spindle assembly checkpoint-related protein, promotes the endometrial endometrioid carcinoma progression. We found that both messenger RNA and protein levels of tyrosine threonine kinase in endometrial endometrioid carcinoma tissues are higher than those in normal endometrial tissues, and its expression is associated with tumor stages. Genetic depletion of tyrosine threonine kinase by RNA interference in two endometrial endometrioid carcinoma cell lines significantly inhibits cell proliferation and induces apoptosis. Mechanistically, depletion of tyrosine threonine kinase induces G2/M cell cycle arrest and triggers caspase-dependent cell apoptosis. Collectively, tyrosine threonine kinase is significantly upregulated in endometrial endometrioid carcinoma, and downregulation of tyrosine threonine kinase can suppress endometrial endometrioid carcinoma cell proliferation and promote apoptosis via G2/M cell cycle arrest. Our study demonstrates that tyrosine threonine kinase can be a potential therapeutic target for endometrial endometrioid carcinoma treatment.