Prognostic value of TOP2A in bladder urothelial carcinoma and potential molecular mechanisms

Yuan

J Cellular Molecular Medi

et al. 2019

The precision evaluation of prognosis is crucial for clinical treatment decision of bladder cancer (BCa). Therefore, establishing an effective prognostic model for BCa has significant clinical implications. We performed WGCNA and DEG screening to initially identify the candidate genes. The candidate genes were applied to construct a LASSO Cox regression analysis model. The effectiveness and accuracy of the prognostic model were tested by internal/external validation and pan-cancer validation and time-dependent ROC. Additionally, a nomogram based on the parameter selected from univariate and multivariate cox regression analysis was constructed.Eight genes were eventually screened out as progression-related differentially expressed candidates in BCa. LASSO Cox regression analysis identified 3 genes to build up the outcome model in E-MTAB-4321 and the outcome model had good performance in predicting patient progress free survival of BCa patients in discovery and test set. Subsequently, another three datasets also have a good predictive value for BCa patients' OS and DFS. Time-dependent ROC indicated an ideal predictive accuracy of the outcome model. Meanwhile, the nomogram showed a good performance and clinical utility. In addition, the prognostic model also exhibits good performance in pan-cancer patients. Our outcome model was the first prognosis model for human bladder cancer progression prediction via integrative bioinformatics analysis, which may aid in clinical decision-making. K E Y W O R D S bladder cancer, Gene Expression Omnibus (GEO), LASSO, prognosis, WGCNA S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Xiong Y, Yuan L, Xiong J, et al. An outcome model for human bladder cancer: A comprehensive study based on weighted gene co-expression network analysis.

Section: Discussionmentioning

confidence: 55%

An outcome model for human bladder cancer: A comprehensive study based on weighted gene co‐expression network analysis

Yuan

J Cellular Molecular Medi

et al. 2019

“…As a DNA replication-and cell division-regulating enzyme, TOP2A is the main target of several anticancer drugs, such as doxorubicin, etoposide, and mitoxantrone (50). High expression levels of TOP2A in various types of tumors, such as lung adenocarcinoma, bladder urothelial carcinoma, breast, prostate and colon cancer, indicates a poor prognosis (51)(52)(53)(54)(55), although this has not been previously reported in HCC. However, Panvichian et al (56) have demonstrated that the high expression of TOP2A in HCC is associated with the high expression of Ki67, and Ki-67 expression has been found to correlate with tumor growth rate and poor prognosis in HCC (57), which indicates that TOP2A is a potential target for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-α (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase IIα. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319x10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40x10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

Technol Cancer Res Treat

“… 32 It has been reported that this topoisomerase could function as a target for anti-cancer therapy, and a variety of mutations in this gene are associated with the development of drug resistance. 33 - 35 Moreover, TOP2A is commonly amplified in thyroid cancer according to the COSMIC and cBioPortal databases, and the mutational frequency is approximately 1%. CDC20 encodes a protein that acts as a regulatory factor for multiple mitotic processes 36 ; this protein has been reported in various malignancies and plays a vital role in tumorigenesis and progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes in Anaplastic Thyroid Carcinoma: Evidence From Bioinformatics Analysis

Zhu

et al. 2020

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer that results in fatal clinical outcomes; the pathogenesis of this life-threatening disease has yet to be fully elucidated. This study aims to identify the hub genes of ATC that may play key roles in ATC development and could serve as prognostic biomarkers or therapeutic targets. Two microarray datasets (GSE33630 and GSE53072) were obtained from the Gene Expression Omnibus database; these sets included 16 ATC and 49 normal thyroid samples. Differential expression analyses were performed for each dataset, and 420 genes were screened as common differentially expressed genes using the robust rank aggregation method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential bio-functions of these differentially expressed genes (DEGs). The terms and enriched pathways were primarily associated with cell cycle, cell adhesion, and cancer-related signaling pathways. Furthermore, a protein-protein interaction network of DEG expression products was constructed using Cytoscape. Based on the whole network, we identified 7 hub genes that included CDK1, TOP2A, CDC20, KIF11, CCNA2, NUSAP1, and KIF2C. The expression levels of these hub genes were validated using quantitative polymerase chain reaction analyses of clinical specimens. In conclusion, the present study identified several key genes that are involved in ATC development and provides novel insights into the understanding of the molecular mechanisms of ATC development.