Paired box 2 promotes progression of endometrial cancer via regulating cell cycle pathway

Wang, Jieyu; Nan, Jun; Lyv, Tianjiao; Wang, Chao; Tao, Xiang; Wong, KwongKwok; Li, Qin; Feng, Weiwei

doi:10.7150/jca.22418

Cited by 12 publications

(11 citation statements)

References 31 publications

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“…In this study, four cases (two hyperplasia without atypia and two proliferative endometrium) were diagnosed by using ZW-FA as potentially precancerous or malignant lesions. As Senol et al reported previously, 29.4% of endometrial hyperplasia was found with FR-α expression and 6.7% was found with high FR-α expression, and endometrial cancer was found with signi cantly high FR-α expression [33]. Consistently in this study, signi cantly higher FR-α expression was encountered in endometrial carcinomas in comparison to hyperplasia and normal endometrium.…”

Section: Discussionsupporting

confidence: 90%

A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

Liang

Tuo

Zhao

et al. 2020

Preprint

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Background Endometrial cancer is the second-most prevalent cancer after breast cancer. Endometrial cytology test is a new diagnosis method for endometrial lesions. However, some unresolved issues limited the application of endometrial cytology test (ECT) in early diagnosis and screening of endometrial cancer. Evidence suggests that FRα is overexpressed in various solid tumors such as endometrial cancer, breast carcinoma, ovarian cancer and so on. Based on the expression of FR-α, the agent used in intraoperative imaging, FRα-targeting antibody drugs and diagnosis were developed previously. Nevertheless, research regarding agents used in the diagnosis of endometrial cancer is rarely carried out yet. Methods To obtain a promising and efficient method for in vitro and screening diagnosis of endometrial cytology, we performed the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. Results The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. Conclusions ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions. This research offers a promising and efficient method for in vitro and screening diagnosis of endometrial cytology. Trial registration: ChiCTR1800020123. Registered December 15, 2018.

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Section: Discussionsupporting

confidence: 90%

A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

Liang

Tuo

Zhao

et al. 2020

Preprint

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“…At present, there are few studies regarding the role of CCNB1, CCNB2, and CCNA2 in EC. Wang J. et al, 2018 found that CCNA2 expression was high and was positively correlated with histological grades, where a higher expression of CCNA2 was associated with worse differentiation in endometrial adenocarcinoma. CDK1 is a target gene of miR-1271, human paired box 2 and LncRNA ABHD11-AS1 and regulates endometrial carcinoma cell line proliferation, invasion, migration, apoptosis, and other mobility factors (Li et al, 2017; Liu Y. et al, 2018; Wang J. et al, 2018).…”

Section: Discussionmentioning

confidence: 90%

“…Wang J. et al, 2018 found that CCNA2 expression was high and was positively correlated with histological grades, where a higher expression of CCNA2 was associated with worse differentiation in endometrial adenocarcinoma. CDK1 is a target gene of miR-1271, human paired box 2 and LncRNA ABHD11-AS1 and regulates endometrial carcinoma cell line proliferation, invasion, migration, apoptosis, and other mobility factors (Li et al, 2017; Liu Y. et al, 2018; Wang J. et al, 2018). In vulvar squamous cell carcinoma, elevated levels of CDK1 were found in patients with advanced tumor behaviors and aggressive features (Wang Z. et al, 2015).…”

Section: Discussionmentioning

confidence: 90%

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

Liu

Lin

2019

Front. Genet.

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Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Methods and Results: An mRNA sequencing dataset, corresponding survival data and expression profiling of an array of EC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Common differentially expressed genes (DEGs) were identified based on sequencing and expression as given in the profiling dataset. Pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction network was established using the string online database in order to identify hub genes. Univariate and multivariable Cox regression analyses were used to screen prognostic DEGs and to construct a prognostic signature. Survival analysis based on the prognostic signature was performed on TCGA EC dataset. A total of 255 common DEGs were found and 11 hub genes (TOP2A, CDK1, CCNB1, CCNB2, AURKA, PCNA, CCNA2, BIRC5, NDC80, CDC20, and BUB1BA) that may be closely related to the pathogenesis of EC were identified. A panel of 7 DEG signatures consisting of PHLDA2, GGH, ESPL1, FAM184A, KIAA1644, ESPL1, and TRPM4 were constructed. The signature performed well for prognosis prediction (p < 0.001) and time-dependent receiver-operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.797, 0.734, 0.729, and 0.647 for 1, 3, 5, and 10-year overall survival (OS) prediction, respectively. Conclusion: This study identified potential genes that may be involved in the pathophysiology of EC and constructed a novel gene expression signature for EC risk stratification and prognosis prediction.

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“…The Rac1 pathway is closely associated with the invasion and metastasis of ES; a previous study has demonstrated that Erb-B2 receptor tyrosine kinase 4 mediates Rac1 GTPase activation and enhances ES invasion and metastasis in vivo by activating the PI3K-Akt cascade and focal adhesion kinase (40). The cell cycle pathway serves a key role in the malignant proliferation process in breast (41), endometrial (42), bladder (43) and gastric (44) cancer. A recent study reported that the cell cycle pathway is also involved in the ES proliferation process (45).…”

Section: Discussionmentioning

confidence: 99%

Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma

et al. 2019

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Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES. mRNA expression profile chip data sets GSE17674, GSE17679 and GSE45544 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the R software limma package, and functional and pathway enrichment analyses were performed using the enrichplot package and GSEA software. The NetworkAnalyst online tool, as well as Cytoscape and its plug-ins cytoHubba and NetworkAnalyzer, were used to construct a protein-protein interaction network (PPI) and conduct module analysis to screen key (hub) genes. LABSO COX regression and overall survival (OS) analysis of the Hub genes were performed. A total of 211 DEGs were obtained by integrating and analyzing the three data sets. The functions and pathways of the DEGs were mainly associated with the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes, as well as the Rac1, cell cycle and P53 signaling pathways. A total of one important module and 20 hub genes were screened from the PPI network using the Maximum Correlation Criteria algorithm of cytoHubba. LASSO COX regression results revealed that titin (TTN), fast skeletal muscle troponin T, skeletal muscle actin α-actin, nebulin, troponin C type 2 (fast), myosin light-chain 3 (MYL3), slow skeletal muscle troponin T (TNNT1), myosin-binding protein C1 slow-type, tropomyosin 3 and myosin heavy-chain 7 were associated with prognosis in patients with ES. The Kaplan-Meier curves demonstrated that high mRNA expression levels of TNNT1 (P<0.001), TTN (P=0.049), titin-cap (P=0.04), tropomodulin 1 (P=0.011), troponin I2 fast skeletal type (P=0.021) and MYL3 (P=0.017) were associated with poor OS in patients with ES. In conclusion, the DEGs identified in the present study may be key genes in the pathogenesis of ES, three of which, namely TNNT1, TTN and MYL3, may be potential prognostic biomarkers for ES.

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Paired box 2 promotes progression of endometrial cancer via regulating cell cycle pathway

Cited by 12 publications

References 31 publications

A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma

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