Impact of an innovative bundled payment to TB health care providers in China: an economic simulation analysis.

BACKGROUND: Tuberculosis is the second most deadly infectious disease after COVID-19 and the 13th leading cause of death worldwide. Among the 30 countries with a high burden of TB, China ranks third in the estimated number of TB cases. China is in the top four of 75 countries with a deficit in funding for TB strategic plans. To reduce costs and improve the effectiveness of TB treatment in China, the NHSA developed an innovative BP method. This study aimed to simulate the effects of this payment approach on different stakeholders, reduce the economic burden on TB patients, improve the quality of medical services, facilitate policy optimization, and offer a model for health care payment reforms that can be referenced by other regions throughout the world. METHODS: We developed a simulation model based on a decision tree analysis to project the expected effects of the payment method on the potential financial impacts on different stakeholders. Our analysis mainly focused on comparing changes in health care costs before and after receiving BPs for TB patients with Medicare in the pilot areas. The data that were used for the analysis included the TB service claim records for 2019-2021 from the health insurance agency, TB prevalence data from the local Centre for Disease Control, and health care facilities' revenue and expenditure data from the Statistic Yearbook. A Monte Carlo randomized simulation model was used to estimate the results. RESULTS: After adopting the innovative BP method, for each TB patient per year, the total annual expenditure was estimated to decrease from $2,523.28 to $2,088.89, which is a reduction of $434.39 (17.22%). The TB patient out-of-pocket expenditure was expected to decrease from $1,249.02 to $1,034.00, which is a reduction of $215.02 (17.22%). The health care provider's revenue decreased from $2,523.28 to $2,308.26, but the health care provider/institution's revenue-expenditure ratio increased from -6.09% to 9.50%. CONCLUSIONS: This study highlights the potential of BPs to improve medical outcomes and control the costs associated with TB treatment. It demonstrates its feasibility and advantages in enhancing the coordination and sustainability of medical services, thus offering valuable insights for global health care payment reform.

Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation.

PURPOSE: The purpose of this study was to clarify the effect of ZC3H13 on the growth of papillary thyroid carcinoma (PTC). METHODS: Firstly, we used qRT-PCR and Western blot to compare the difference in the expression of ZC3H13 between normal thyroid epithelial cells and PTC cell lines. Then, ZC3H13 overexpression/knockout thyroid cancer cells were constructed by lentivirus transfection, and the effects of overexpression of ZC3H13 on the proliferation, migration and invasion of PTC cells were detected by CCK8 and transwell experiments. Lastly, MeRIP-qPCR, RIP and o Actinomycin D were used to verify that ZC3H13 regulated the expression of downstream target gene IQGAP1 through m6A modification. RESULTS: ZC3H13 expression was decreased in PTC cell lines BCPAP, KTC-1, k1, HTH83, and TPC-1. Proliferation, invasion, and migration of PTC cells were inhibited by overexpressed ZC3H13 but increased by knockdown of ZC3H13. IQGAP1 expression was suppressed by ZC3H13 overexpression but enhanced by ZC3H13 knockdown. In ZC3H13-overexpressed PTC cells, the m6A level of IQGAP1 mRNA was increased, and the IQGAP1 mRNA expression was decreased with the increasing time of Actinomycin D treatment. YTHDF2 enriched more IQGAP1 mRNA than IgG and knockdown of YTHDF2 reversed the effect of ZC3H13 overexpression on IQGAP1 mRNA stability. The xenograft tumor experiment in nude mice confirmed that the overexpression of ZC3H13 inhibited tumor growth, while overexpression of IQGAP1 could reverse the inhibitory effect of ZC3H13 overexpression on tumor growth. CONCLUSION: ZC3H13 mediates IQGAP1 mRNA degradation by promoting m6A modification of IQGAP1 mRNA, this provides a prospective therapeutic target for PTC.

RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, frequently accompanied by metastasis and aerobic glycolysis. Cancer cells adjust their metabolism by modulating the PKM alternative splicing and facilitating PKM2 isoform expression. Therefore, identifying factors and mechanisms that control PKM alternative splicing is significant for overcoming the current challenges in ATC treatment. RESULTS: In this study, the expression of RBX1 was largely enhanced in the ATC tissues. Our clinical tests suggested that high RBX1 expression was significantly related to poor survival. The functional analysis indicated that RBX1 facilitated the metastasis of ATC cells by enhancing the Warburg effect, and PKM2 played a key role in RBX1-mediated aerobic glycolysis. Furthermore, we confirmed that RBX1 regulates PKM alternative splicing and promotes the PKM2-mediated Warburg effect in ATC cells. Moreover, ATC cell migration and aerobic glycolysis induced by RBX1-mediated PKM alternative splicing are dependent on the destruction of the SMAR1/HDAC6 complex. RBX1, as an E3 ubiquitin ligase, degrades SMAR1 in ATC through the ubiquitin-proteasome pathway. CONCLUSION: Overall, our study identified the mechanism underlying the regulation of PKM alternative splicing in ATC cells for the first time and provides evidence about the effect of RBX1 on cellular adaptation to metabolic stress.

TRIM16 promotes aerobic glycolysis and pancreatic cancer metastasis by modulating the NIK-SIX1 axis in a ligase-independent manner.

Enhanced aerobic glycolysis contributes to the metastasis of pancreatic cancer metastasis, but the mechanism underlying the abnormal activation of glycolysis has not been fully elucidated. The E3 ligase tripartite motif 16 (TRIM16) is involved in the progression of many cancers. However, the role of and molecular mechanism by which TRIM16 acts in pancreatic cancer are unclear. In this study, we report that TRIM16 was significantly upregulated in pancreatic cancer tissues, and high expression of TRIM16 was associated with poor prognosis in patients with pancreatic cancer. Multivariate analyses showed that TRIM16 was an independent predictor of poor outcomes among patients with pancreatic cancer. In addition, in vitro and in vivo evidence showed that TRIM16 promoted pancreatic cancer cell metastasis by enhancing glycolysis. Furthermore, we revealed that TRIM16 controlled glycolysis and pancreatic cancer cell's metastasis by regulating sine oculis homeobox 1 (SIX1), an important transcription factor that promotes glycolysis. TRIM16 upregulated SIX1 by inhibiting its ubiquitination and degradation, which was mediated by NF-κB-inducing kinase (NIK), an upstream regulator of SIX1. Hence, NIK inhibitor can suppress SIX1 expression, glycolysis and metastasis in TRIM16-overexpressing pancreatic cancer cells. Mechanistic investigations demonstrated that TRIM16 competed with NIK's E3 ligase, TNF receptor-associated factor 3 (TRAF3), at the ISIIAQA sequence motif of NIK, and then stabilized NIK protein. Our study identified the TRIM16-NIK-SIX1 axis as a critical regulatory pathway in aerobic glycolysis and pancreatic cancer metastasis, indicating that this axis can be an excellent therapeutic target for curing pancreatic cancer.

LGALS2 suppresses the progression of papillary thyroid carcinoma by regulating the PI3K/AKT pathway.

Background: The galectin 2 (LGALS2) protein has been shown to be associated with the pathogenic progression of a range of cancer types, yet its role in papillary thyroid carcinoma (PTC) remains poorly defined. Accordingly, the present study was conducted to address this gap in the literature. Methods: Eighty pairs of tumor and paracancerous tissues from PTC patients were collected. Western immunoblotting and real-time quantitative polymerase chain reaction (qPCR) were used to compare LGALS2 expression levels in tumor and paracancerous tissues from PTC patients. An LGALS2 overexpression construct was produced by inserting the coding sequence for this gene into a pcDNA4.0 vector, and LGALS2-specific and control siRNA constructs were obtained. CCK-8, EdU uptake, and apoptotic assays were used to gauge the role of LGALS2 as a regulator of in vitro PTC cell growth and apoptosis, while its in vivo role was assessed using a murine xenograft model. Results: LGALS2 mRNA and protein levels were reduced in both PTC tumors and cell lines, and the expression of this gene was related to PTC patient prognosis and clinicopathological features. LGALS2 knockdown enhanced PTC cell proliferative activity while decreasing the sensitivity of these cells to apoptotic death. In contrast, the opposite effect was evident following LGALS2 overexpression in vitro and in vivo. LGALS2 also suppressed the progression of PTC by its ability to induce phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway activation. Conclusions: These data indicate that LGALS2 suppresses PTC progression via PI3K/AKT pathway activation, suggesting that LGALS2 offers value as a treatment target for patients with this cancer type.

The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2.

Ataxin-3 (ATXN3) is a ubiquitous deubiquitinating enzyme that plays an essential role in the carcinogenesis of numerous tumors and stabilizes the expression of substrates by deubiquitination. However, the functional role of ATXN3 in anaplastic thyroid carcinoma (ATC) remains unknown. In this research, we report that ATXN3 was overexpressed in ATC compared to that in paracancerous samples. Moreover, various gain/loss functional assays were performed to indicate that ATXN3 overexpression enhanced ATC cell proliferation and metastasis. We also found that ATXN3 and eukaryotic translation initiation factor 5A2 (EIF5A2) protein levels in ATC tissues are positively correlated, and ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. Mechanistically, ATXN3 promotes EIF5A2 expression by directly binding to EIF5A2 to reduce its ubiquitination and degradation. Therefore, for the first time, we clarified the role of ATXN3 in the carcinogenesis of ATC cells, which provides novel insights into potential therapeutic targets for ATC progression.

RING-finger protein 6 enhances c-Myc-mediated Warburg effect by promoting MAD1 degradation to facilitate pancreatic cancer metastasis.

Aerobic glycolysis (the Warburg effect) promotes tumor metastasis; hence, drugs targeting its regulators are being developed. c-Myc, a critical transcription factor that regulates the Warburg effect, is involved in the tumorigenesis of many cancers, including pancreatic cancer (PC). However, the upstream regulating mechanisms of c-Myc in PC are unclear. Herein, we reported that E3 ubiquitin ligase RING-finger protein 6 (RNF6) was upregulated in PC tissues, and an elevated RNF6 level was closely associated with metastasis and poor prognosis in patients with PC. In functional experiments, RNF6 over-expression accelerated the metastatic ability of PC cells, whereas RNF6 knockdown impaired PC cell motility and invasiveness along with metastasis in an orthotopic mouse model. Furthermore, we found that RNF6 promoted PC cell metastasis by enhancing c-Myc-mediated aerobic glycolysis. Mechanistically, RNF6 increased the expression level of c-Myc by catalyzing the ubiquitination of Max-dimerization protein-1 (MAD1), a cellular antagonist of c-Myc. Lastly, RNF6 promoted the degradation of MAD1 via the ubiquitin-proteasome pathway, and this reduction in the MAD1 levels enabled c-Myc to promote the Warburg effect in PC. Our results demonstrate that RNF6 may be a novel biomarker in PC carcinogenesis, thereby indicating that targeting the RNF6/MAD1/c-Myc axis is a potential strategy for PC therapy.

Minimally Invasive Video-Assisted Surgical Management for Parapharyngeal Metastases From Papillary Thyroid Carcinoma: A Case Series Report.

Background: Papillary thyroid carcinoma (PTC) is the most prevalent cancer type in the endocrine system. Metastases to parapharyngeal lymph nodes (PPLNs) are rare. Herein, we reported a case series of PTC patients with PPLN metastases operated on by using the minimally invasive video-assisted (MIVA) technique to evaluate the safety and effectiveness of this technique. Method: In this single-institutional study, six consecutive PTC patients with PPLN metastases between January 2012 and July 2018 were enrolled. All PPLNs were managed by the MIVA technique. Result: Six patients (three women and three men) who underwent surgery were enrolled in the current study. The median age of patients was 40.5 years (39-66). Five patients (83.3%) were diagnosed with primary PTC with PPLN metastases, and one patient had PTC recurrence in the PPLNs 17 years after her first PTC surgery. Surgical treatment was successful in all patients, and the median operative time and bleeding volume were 185 (100-280) min and 85 (30-120) ml, respectively. None of the patients experienced post-operative complications except for one patient who experienced dysphagia, which resolved within 3 months. During a median follow-up of 15 months (10-31), none of the patients exhibited recurrence or persistent disease. Conclusion: The MIVA transcervical approach was technically feasible and reliable, with less invasiveness for PTC patients with PPLN metastases. Future studies are needed to accumulate more experience, investigate the indications of the technique, and determine the long-term oncological safety.

Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway.

Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan-Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

Long non-coding RNA LINC00662 promotes proliferation and migration in oral squamous cell carcinoma.

BACKGROUND: Although increasing evidence has demonstrated important roles for long non-coding RNAs (lncRNAs) in cancer development, their functions in oral squamous cell carcinoma (OSCC) growth remain largely unknown. Therefore, we aimed to investigate the role of LINC00662 in OSCC. METHODS: The expression of LINC00662 in 61 OSCC tissues and four OSCC cell lines were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and EdU staining methods. Migration and invasion abilities were analyzed using transwell and wound healing assay. Cell cycle distribution and apoptosis rate were evaluated by flow cytometry. Western blot method was performed to detect protein expression. RESULTS: We found that the expression of LINC00662 was significantly increased in OSCC tissues, and a higher expression of LINC00662 was detected in larger tumor size, higher stage tumors and with lymph node metastasis. Moreover, overexpression of LINC00662 induced OSCC cell proliferation, increased migration and invasion abilities, and suppressed cell apoptosis. Knockdown of LINC00662 decreased the proliferation, migration, and invasion abilities of OSCC cell, and induced apoptosis. Furthermore, LINC00662 regulated the Wnt/ß-catenin pathway. CONCLUSION: Our data indicate that LINC00662 may represent a novel indicator of OSCC and may be a potential therapeutic target for diagnosis and therapy.

Pretreatment BMI Is Associated with Aggressive Clinicopathological Features of Papillary Thyroid Carcinoma: A Multicenter Study.

OBJECTIVES: The aim of the present study was to analyze the association between pretreatment body mass index (BMI) and the aggressiveness of papillary thyroid carcinoma (PTC) along with its clinical outcomes in a Chinese population with BMI classification for Asians. METHODS: A retrospective, observational study was conducted on patients from two teaching hospitals in China. 1622 classical PTC patients were categorized into four groups according to BMI. RESULTS: We found that increased BMI was associated with extrathyroidal extension, multifocality, the presence of lymph node (LN) metastasis, and advancing TNM stage in PTC patients. Furthermore, compared to patients with normal weight, those in the overweight and obese group exhibited a significantly increased risk of extrathyroidal extension, multifocality, cervical LN metastasis, and advanced TNM stage. 40 and 37 patients experienced persistent and recurrent disease, respectively. No differences regarding persistent disease or recurrence were observed among the BMI groups. CONCLUSION: A higher pretreatment BMI has been strongly associated with aggressive features of PTC according to the BMI classification for Asians. Obesity was not found to be associated with a greater risk of recurrence.

Special role of JUN in papillary thyroid carcinoma based on bioinformatics analysis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignancy in thyroid tissue, and the number of patients with PTC has been increasing in recent years. Discovering the mechanism of PTC genesis and progression and finding new potential diagnostic biomarkers/therapeutic target genes of PTC are of great significance. METHODS: In this work, the datasets GSE3467 and GSE3678 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified with the limma package in R. GO function and KEGG pathway enrichment were conducted with DAVID tool. The interaction network of the DEGs and other genes was performed with Cytoscape plugin BisoGenet, while clustering analysis was performed with Cytoscape plugin ClusterOne. RESULTS: A total of 1800 overlapped DEGs were detected in two datasets. Enrichment analysis of the DEGs found that the top three enriched GO terms in three ontologies and four significantly enriched KEGG pathways were mainly concerned with intercellular junction and extracellular matrix components. Interaction network analysis found that transcription factor hepatocyte nuclear factor 4, alpha (HNF4A) and DEG JUN had higher connection degrees. Clustering analysis indicated that two function modules, in which JUN was playing a central role, were highly relevant to PTC genesis and progression. CONCLUSIONS: JUN may be used as a specific diagnostic biomarker/therapeutic molecular target of PTC. However, further experiments are still needed to confirm our results.

Preoperative albumin/globulin ratio has predictive value for patients with laryngeal squamous cell carcinoma.

This study evaluated the predictive value of the preoperative albumin/globulin ratio (AGR) in laryngeal squamous cell carcinoma (LSCC) retrospectively, which has not been reported before. The current study enrolled 241 newly diagnosed LSCC patients in the Second Affiliated Hospital of Nanchang University between January 2005 and December 2010. The optimal AGR cut-off value for overall survival (OS) was determined to be 1.28. Univariate survival analysis identified sex, low AGR, T classification, histological grade and nodal metastasis as factors associated with poor OS. Additionally, a low AGR, T classification, nodal metastasis, and histological grade were associated with poor disease-free survival (DFS) in LSCC patients. In multivariate survival analysis, nodal metastasis and a low AGR remained significant for OS and DFS. Our preliminary study revealed that low preoperative AGR could serve as a valuable and easily-assessed blood-based indicator to predict the prognosis of LSCC patients.

Thymosin beta 10 correlates with lymph node metastases of papillary thyroid carcinoma.

BACKGROUND: Thymosin beta 10 (TMSB10) has recently been recognized as being an important player in the metastatic cascade including tumor angiogenesis, invasion, and metastasis. However, a role for this protein in papillary thyroid carcinoma (PTC) has not yet been established. METHODS: Real-time polymerase chain reaction was used to examine the expression of TMSB10 messenger RNA in 36 cases of thyroid tissue samples: normal thyroid, PTC without lymph node metastases (LNM) and PTC with LNM (n = 12 cases in each subgroup). For immunohistochemistry, 130 patients with PTC were selected during the period of 2004-2005, 91 with and 39 without LNM. Statistical analysis was applied to evaluate the correlation between TMSB10 expression and LNM of PTC. RESULTS: By real-time polymerase chain reaction analysis, the expression of TMSB10 messenger RNA in normal thyroid tissue, PTC without LNM, and PTC with LNM tissue were significantly different (P < 0.0001). On immunohistochemistry analysis of 130 patients with PTC, in which 91 cases had cervical LNM and 69 cases had central neck LNM, high expression levels for TMSB10 were more common in patients with cervical LNM compared with patients without (81% versus 33%, P < 0.001). Similarly, high expression levels of TMSB10 were more common in patients with central neck LNM compared with those without (87.0% versus 44.3%, P < 0.001). CONCLUSIONS: High expression levels of TMSB10 correlated with LNM in PTC, especially in the central neck region. Patients with PTC with low levels of TMSB10 expression may be unlikely to have central neck LNM and could therefore avoid prophylactic central neck dissection.

[Application of lymphatic mapping to recognize and protect parathyroid in thyroid carcinoma surgery by using carbon nanoparticles].

OBJECTIVE: To discuss the role of carbon nanoparticles in the protection of parathyroid during thyroid carcinoma surgery. METHOD: Seventy-two patients with thyroid carcinoma who had initial surgery were randomly divided into two groups: carbon nanoparticles group and the control group. Emulsion of carbon nanoparticles was injected into the thyroid gland of carbon nanoparticles group patients. After thirty minutes,the excision of thyroid carcinoma and VI group neck dissection were performed in carbon nanoparticles group patients, the control group directly underwent operation. The black stained tissue in the dissection specimen of carbon nanoparticles group was separated. The number of total lymph node,metastasis lymph node and parathyroid gland in the tissure black stained or not in two groups were counted respectively. RESULTS: There were 312 lymph nodes in the black stained tissue of central compartment dissection specimen of carbon nanoparticles group. No parathyroid gland was found in the black stained tissue. Fifteen lymph nodes containing four parathyroid glands were found in the non black stained tissue in carbon nanoparticles group while there were 202 lymph nodes containing 13 parathyroid glands in the control group. There were statistical difference between the amount of lymph node in black stain tissue and the specimen of the control group. Parathyroid glands were not stained black,and no parathyroid gland was found in the black-stained tissue. CONCLUSION: The carbon nanoparticles could be used to identify the lymph node and the parathyroid gland for protecting the parathyroid gland in thyroid surgery.

Should level V be included in lateral neck dissection in treating papillary thyroid carcinoma?

BACKGROUND: The study was designed to explore the regular patterns of level V lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC), and to indicate whether level V should be included in the management of lateral neck dissection when treating PTC. METHODS: This retrospective study consisted of 330 patients diagnosed with PTC from January 1994 to July 2009 who underwent an operation that included therapeutic lateral neck dissection (levels II to V). The patterns of lateral neck LNM were analyzed and the relevant risk factors of level V LNM were analyzed with univariate and multivariate analysis, respectively. RESULTS: All the patients underwent lateral neck dissection at levels II to V. The predominant site of metastasis was level III (247/330 (74.8%)), followed by level IV (233/330 (70.6%)), and level II (215/330 (65.3%)). Simultaneous multilevel involvement (level II, III, and IV) of lymphatic metastases presented in 46.1% (152/330) of the cases. Level V showed 28.8% (95/330) of nodal metastasis. Multivariate analysis showed that level V LNM was significantly associated with location (whole thyroid), gross extrathyroidal extension and simultaneous multilevel involvement (level II, III and IV). (P <0.05). CONCLUSIONS: Due to relatively high rate of level V involvement and its correlation with location (whole thyroid), gross extrathyroidal extension and multilevel involvement, we consider that it may be more rational to include level V in the therapeutic lateral neck dissection when treating PTC, especially for those who have any one of these three independent risk factors.

Combination analysis of Bub1 and Mad2 expression in endometrial cancer: act as a prognostic factor in endometrial cancer.

INTRODUCTION: This study aimed to evaluate the diagnostic value of Bub1 and Mad2 together in endometrial cancer. MATERIALS AND METHODS: Sixty-three patients with endometrial cancer, including EECs and NEECs, were examined statistically. Bub1 and Mad2 in patient tissues were detected by indirect streptavidin-biotin-peroxidase complex method. RESULTS: 39 cases (61.9 %) were in clinical stage I, 17 cases (27 %) in stage II, 5 (7.9 %) in stage III and 2 cases (3.2 %) in stage IV. Bub1 positive and Mad2 positive rate were identified in 18 and 54 patients. The lower positive of Bub1 and higher positive rate of Mad2 were related to clinical stage and histological grade of endometrial cancer (P = 0.009, 0.002, respectively), especially in NEECs. The expression of Bub1 was negatively correlated with Mad2 and Mtp53 (both P < 0.05). The expression of Mad2 with Mtp53 was positively correlated (P < 0.05). Statistically significant difference between Bub1/Mad2 expression and survival was discovered in endometrial cancer. Specificity and sensitivity of combination between Bub1 negative and Mad2 positive cases were higher than those alone in NEEC subtype. Bub1 and Mad2 are associated with histological differentiation, clinical stage and decreased postoperative survival in endometrial cancer. CONCLUSIONS: The combination analysis of Bub1 and Mad2 might be the valuable prognostic, even diagnostic clinicopathologic factor which can be applicable in routine examination.