Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer.

BACKGROUND: Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood. METHODS: Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells. RESULTS: We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial-mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel. CONCLUSION: Our findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.

A review on the role of cyclin dependent kinases in cancers.

The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

BACKGROUND: L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. METHODS: We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. RESULTS: Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. CONCLUSION: L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

Molecular-targeted therapies and precision medicine for endometrial cancer.

The overall survival rate of patients with early-stage endometrial cancer is relatively high; however, there are few treatment options for patients with advanced or recurrent endometrial cancer, and the prognosis of such patients remains poor. Recent progress in molecular-targeted therapies demonstrated that they have the potential to improve the long-term survival of cancer patients with appropriate biomarkers. However, the median progression-free survival of patients who received single-agent molecular-targeted therapy was <5 months, and the development of molecular-targeted therapies for endometrial cancer patients is urgently needed. This review highlights the previous efforts, including antiangiogenesis therapy, PI3K/AKT/mTOR pathway inhibitor treatment and epidermal growth factor receptor inhibitor treatment and reports on ongoing phase 2 clinical trials, including immune checkpoint inhibitor and PARP inhibitor. We also summarized the genetic background of endometrial cancer according to The Cancer Genome Atlas data and considered the theoretical background for future efforts to prolong the survival of patients with refractory endometrial cancer and for other interesting challenges.

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women.

Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.

KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells.

KLF4 is a transcriptional factor that can function either as a tumor suppressor or oncogene in cancer based on its cellular context. We recently demonstrated that KLF4 was a tumor suppressor in ovarian cancer cells by inhibiting the epithelial to mesenchymal transition. Here we report that KLF4 expression was downregulated in ovarian cancer tissue compared to normal ovarian tissue, and low KLF4 expression correlated with high risk ovarian carcinoma and poor patient survival. Enforced KLF4 expression by lentiviral transduction sensitized ovarian cancer cells to the effects of the chemotherapy drugs, paclitaxel and cisplatin. Treatment of ovarian cancer cells with APTO-253, a small molecule inducer of KLF4, enhanced the efficacy of both chemotherapy drugs. KLF4 expression mediated by lentiviral vector or induced by APTO-253 resulted in G1 phase arrest in ovarian cancer cells. Our results demonstrate that for the first time that inducing KLF4 expression with APTO-253 is a novel therapeutic strategy for treating ovarian cancer.

Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer.

Krüppel-like factor 17 (KLF17), a member of the KLF transcription factor family, has been shown to inhibit the epithelial-mesenchymal transition (EMT) and tumor growth. However, the expression, the cellular function and the mechanism of KLF17 in endometrioid endometrial cancer (EEC; a dominant type of endometrial cancer) remain elusive. Here, we report that among the KLF family members, KLF17 was consistently upregulated in EEC cell lines compared with immortalized endometrial epithelial cells. Overexpression of KLF17 in EEC cell lines induced EMT and promoted cell invasion and drug resistance, resulting in increased expression of TWIST1. In contrast, KLF17 suppression reversed EMT, diminished cell invasion, restored drug sensitivity and suppressed TWIST1 expression. Luciferase assays, site-directed mutagenesis and transcription factor DNA-binding analysis demonstrated that KLF17 transactivates TWIST1 expression by directly binding to the TWIST1 promoter. Knockdown of TWIST1 prevented KLF17-induced EMT. Consistent with these results, both KLF17 and TWIST1 levels were found to be elevated in EECs compared with normal tissues. KLF17 expression positively correlated with tumor grade but inversely correlated with estrogen and progesterone receptor expression. Thus, KLF17 may have an oncogenic role during EEC progression via initiating EMT through the regulation of TWIST1.

MicroRNA-106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines.

Type II endometrial carcinoma is an aggressive subtype of endometrial cancer (EC). TWIST1, a helix-loop-helix transcription regulator, is known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) also serve as important regulators of EMT and metastasis by regulating EMT-related genes. In this study, we sought to explore the role of TWIST1 in inducing EMT in representative type II EC cell lines, and to determine the miRNAs involved in regulating TWIST1 gene expression. Functional analysis suggested that TWIST1 contributes to the EMT phenotypes of EC cells, as evidenced by the acquisition of fibroblast-like properties, enhanced invasiveness, and induction of an EN-switch (downregulation of epithelial marker E-cadherin and upregulation of mesenchymal marker N-cadherin). Conversely, silencing of TWIST1 by siRNA inhibited cell invasion and the mesenchymal phenotype, which was accompanied by a reversion of the EN-switch. We also observed a novel post-transcriptional regulatory mechanism of TWIST1 expression mediated by miR-106b via its direct interaction with TWIST1 mRNAs at the 3'-untranslated region. Our data suggest that TWIST1 is a critical inducer of EMT in invasive EC cells and that miR-106b could suppress EC cell invasion by downregulating TWIST1 expression.

The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer.

Activation of the PI3K/AKT pathway, a common mechanism in all subtypes of endometrial cancers (endometrioid and non-endometrioid tumors), has important roles in contributing to epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features. MicroRNAs (miRNAs) are small non-coding RNA molecules that concurrently affect multiple target genes, and regulate a wide range of genes involved in modulating EMT and CSC properties. Here we overview the recent advances revealing the impact of miRNAs on EMT and CSC phenotypes in tumors including endometrial cancer via regulating PI3K/AKT pathway. MiRNAs are crucial mediators of EMT and CSC through targeting PTEN-PI3K-AKT-mTOR axis. In endometrial cancer cells, miRNAs can activate or attenuate EMT and CSC by targeting PTEN and other EMT-associated genes, such as Twist1, ZEB1 and BMI-1. More detailed studies of miRNAs will deepen our understanding of the molecular basis underlying PI3K/AKT-induced endometrial cancer initiation and progression. Targeting key signaling components of PI3K/AKT pathway by restoring or inhibiting miRNA function holds promise as a potential therapeutic approach to suppress EMT and CSC in endometrial cancer.

Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials.

PURPOSE: The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer. METHODS: A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location. RESULTS: Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA. CONCLUSION: Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

Association of systemic inflammation markers in cancer mortality with diabetes: evidence from National Health and Nutrition Examination Survey.

AIMS: Inflammation plays a crucial role in the interconnection between diabetes and cancer. Our study seeks to investigate the predictive value of inflammatory indices concerning overall survival (OS) among diabetic cancer patients. METHODS: We analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. Using four immune-related markers, we employed the log-rank method, multivariate Cox regression, and subgroup analysis to explore the predictive capacity of these markers for OS among adult individuals with diabetes and cancer. RESULTS: Our study identified four systemic immune-inflammatory indices that demonstrated significant predictive potential for OS among diabetic cancer patients, namely systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (all p values < 0.05). Notably, these inflammatory biomarkers still maintain their predictive value after adjusting potential confounding factors. The analysis using restrictive cubic splines revealed significant non-linear relationships between inflammatory biomarkers and OS. CONCLUSION: The findings presented in this study underscore the potential of inflammatory markers as prognostic indicators and their crucial role in enhancing risk assessment for diabetic patients with cancer.

The prognostic analysis and a machine-learning based disease-specific survival state model in pulmonary large-cell neuroendocrine carcinomas.

Background: Pulmonary large-cell neuroendocrine carcinoma (PLCNEC) is a rare and highly malignant lung cancer. Due to the paucity of data from clinical studies, its clinical characteristics and treatment remain controversial. The present study explored factors influencing the prognosis and survival outcomes of patients with PLCNEC and developed a dependable prognostic model using machine learning. Methods: The clinical data of PLCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. A total of 2,897 PLCNEC patients were enrolled and univariate and multivariate Cox regression analyses were performed to explore independent prognostic factors for disease-specific survival (DSS). Ten machine learning algorithms were utilized to predict the 2-year survival. The clinicopathological data collected from The First Affiliated Hospital of Sun Yat-sen University between 2010 and 2022 were used to test the trained machine. Results: Sex [hazard ratio (HR) 1.168, 95% confidence interval (CI): 1.063-1.284], age (HR 1.262, 95% CI: 1.144-1.391), surgery (HR 0.481, 95% CI: 0.413-0.559), chemotherapy (HR 0.450, 95% CI: 0.404-0.501), bone metastasis (HR 1.284, 95% CI: 1.124-1.466), brain metastasis (HR 1.167, 95% CI: 1.023-1.331), liver metastasis (HR 1.223, 95% CI: 1.069-1.399), American Joint Committee on Cancer-Node (AJCC-N), and tumor stage were independent prognostic factors. The gradient boosting decision tree (GBDT) performed better than other models, with an F1-score of 0.791 and an area under the curve of 0.831. Conclusions: Male, age ≥65 years, distant metastasis to the bone, liver, and brain are associated with a worse prognosis in PLCNEC patients, while surgery and chemotherapy are associated with improved prognosis. GBDT showed promising performance in predicting 2-year survival, which can serve as a valuable reference for clinical diagnosis and treatment of PLCNEC.

Relationship between hemoglobin and lung cancer: evidence from Mendelian randomization and National Health and Nutrition Examination Survey.

BACKGROUND: Lung cancer is the primary cause of cancer-related mortality worldwide. Hemoglobin (Hb) represents the most widely utilized test parameter in clinical settings. However, few articles have examined the causal relationship between Hb concentration and lung cancer incidence. METHODS: Mendelian randomization (MR) was first conducted to investigate the potential causality between Hb and lung cancer. Sensitivity analyses were applied to validate the reliability of MR results. Then, the National Health and Nutrition Examination Survey (NHANES) database was used to verify the effect of Hb on the prognosis of lung cancer. RESULTS: The MR analysis demonstrated that Hb was casually associated with the decreased risk of lung cancer in the European population (ORIVW 0.84, 95% CI 0.75-0.95, p = 0.006; ORWeighted-median 0.78, 95% CI 0.65-0.94, p = 0.008; ORMR-Egger 0.82, 95% CI 0.64-1.04, p = 0.11). The results from the NHANES database showed that a high value of Hb was associated with better outcomes for patients with lung cancer (HR 0.45, 95% CI 0.26-0.79, p = 1.6E-03). CONCLUSIONS: Our study provides further evidence for the relationship between Hb levels and lung cancer, highlighting the potential significance of Hb as a biomarker for predicting the risk and prognosis of lung cancer.

FHL2 promotes the aggressiveness of lung adenocarcinoma by inhibiting autophagy via activation of the PI3K/AKT/mTOR pathway.

BACKGROUND: Increasing evidence indicates that four and a half LIM domains 2 (FHL2) plays a crucial role in the progression of various cancers. However, the biological functions and molecular mechanism of FHL2 in lung adenocarcinoma (LUAD) remain unclear. METHODS: We evaluated the prognostic value of FHL2 in LUAD using public datasets and further confirmed its prognostic value with our clinical data. The biological functions of FHL2 in LUAD were evaluated by in vitro and in vivo experiments. Pathway analysis and rescue experiments were subsequently performed to explore the molecular mechanism by which FHL2 promoted the progression of LUAD. RESULTS: FHL2 was upregulated in LUAD tissues compared to adjacent normal lung tissues, and FHL2 overexpression was correlated with unfavorable outcomes in patients with LUAD. FHL2 knockdown significantly suppressed the proliferation, migration and invasion of LUAD cells, while FHL2 overexpression had the opposite effect. Mechanistically, FHL2 upregulated the PI3K/AKT/mTOR pathway and subsequently inhibited autophagy in LUAD cells. The effects FHL2 on the proliferation, migration and invasion of LUAD cells are dependent on the inhibition of autophagy, as of induction autophagy attenuated the aggressive phenotype induced by FHL2 overexpression. CONCLUSIONS: FHL2 promotes the progression of LUAD by activating the PI3K/AKT/mTOR pathway and subsequently inhibiting autophagy, which can be exploited as a potential therapeutic target for LUAD.

The significance of N6-methyladenosine-modified non-coding RNAs in different disorders.

N6-methyladenosine (m6A) is the most widespread endogenous modification affecting the expression of eukaryotic mRNA transcripts. Recent studies have shown that the m6A marks within non-coding RNAs can affect their functions and expression in a manner similar to that of mRNA-coding genes. Since non-coding RNAs are involved in the pathophysiology of several disorders, identification of the role of m6A marks in the regulation of expression of non-coding RNAs can open a new era for identifying underlying mechanisms of several disorders and designing novel therapeutic modalities for a variety of disorders, particularly cancers. Moreover, a number of non-coding RNAs can affect m6A levels. In the current review, we discuss the impacts of m6A marks on the expression of non-coding RNAs in the context of different disorders, such as bone, gastrointestinal, neurologic, renal, pulmonary, hepatic and other disorders.

Emerging functions and clinical applications of exosomal microRNAs in diseases.

Exosomes are an important group of extracellular vesicles that transfer several kinds of biomolecules and facilitate cell-cell communication. The content of exosomes, particularly the amounts of microRNA (miRNAs) inside these vesicles, demonstrates a disease-specific pattern reflecting pathogenic processes and may be employed as a diagnostic and prognostic marker. miRNAs may enter recipient cells through exosomes and generate a RISC complex that can cause degradation of the target mRNAs or block translation of their corresponding proteins. Therefore, exosome-derived miRNAs constitute an important mechanism of gene regulation in recipient cells. The miRNA content of exosomes can be used as an important tool in the detection of diverse disorders, particularly cancers. This research field has an important situation in cancer diagnosis. In addition, exosomal microRNAs offer a great deal of promise in the treatment of human disorders. However, there are still certain challenges to be resolved. The most important challenges are as follow: the detection of exosomal miRNAs should be standardized, exosomal miRNAs-associated studies should be conducted in large number of clinical samples, and experiment settings and detection criteria should be consistent across different labs. The goal of this article is to present an overview of the effects of exosome-derived microRNAs on a variety of diseases, including gastrointestinal, pulmonary, neurological, and cardiovascular diseases, with a particular emphasis on malignancies.

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets.

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.

New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the stage migration and survival of endometrial cancer by the revised FIGO 2008 staging system compared with the 1988 staging system. METHODS: A total of 355 patients with endometrial cancer, who underwent complete surgical staging, were enrolled. We compared the surgical stages and survival by FIGO 1988 staging system with those by FIGO 2008 staging system. RESULTS: 2008 FIGO staging system resulted in an increase of stage I patients and decrease of stage II and IIIa patients. The 5-year overall survival (OS) rates for patients with 2008 FIGO stage IA and IB disease were 98.2% and 91.9%, respectively (P = 0.004). Five-year OS rate of new stage II (82.6%) was significantly worse than that of new stage IA (98.2%, P = 0.003). Patients with positive washing cytology alone revealed a 5-year OS rate similar to that of patients with new stage IIIA disease (96.2% vs. 90.9%, respectively; P = 0.53). The 5-year OS rate for patients with stage IIIC1 disease was improved compared with that for patients with stage IIIC2 disease (85.7% vs. 63.0%, respectively; P = 0.08). CONCLUSION: New revised FIGO 2008 staging system for endometrial cancer produced better discrimination in OS outcomes compared with the 1988 system.