Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha (TOP2A) in Human Malignances: A Pan-Cancer Analysis

Author(s):  
Fulai Zhao ◽  
Junli Chang ◽  
Wenyi Wang ◽  
Xingyuan Sun ◽  
Xiaoping Ma ◽  
...  

Abstract Increasing studies have revealed significant associations between TOP2A with oncogenesis and prognosis of human cancers; however, pan-cancer analysis has not been reported. Here, we explored the potential carcinogenic function, the association with clinical outcomes of TOP2A in 33 different human cancers. The results showed that TOP2A was amplified in 32 investigated cancers; TOP2A expression was significantly associated with metastasis of six different cancers, and significantly associated with the survivals of patients in ten different cancers; TOP2A encoded protein was obviously upregulated in five available cancers; phosphorylated TOP2A protein at S1106 was significantly upregulated in all six available cancers. Moreover, TOP2A expression was found to be associated with the cancer-associated immune cell infiltration, including fibroblasts, Tregs and macrophages. In addition, Kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses revealed a most significant association between TOP2A with Wnt signaling pathway, and DNA conformation change. This work provides a comprehensive knowledge of TOP2A in different cancers, including carcinogenic function, prognostic values for metastasis and clinical outcomes.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dazhao Peng ◽  
Cheng Wei ◽  
Xiaoyang Zhang ◽  
Shenghui Li ◽  
Hao Liang ◽  
...  

Abstract Background The function of collagen triple helix repeat containing 1 (CTHRC1) as an oncogene has been reported in a growing number of publications. Bioinformatics methods represent a beneficial approach to examine the mechanism and function of the CTHRC1 gene in the disease process of cancers from a pan-cancer perspective. Methods In this study, using the online databases UCSC, NCBI, HPA, TIMER2, Oncomine, GEPIA, UALCAN, cBioPortal, COSMIC, MEXPRESS, STRING, CCLE, LinkedOmics, GTEx, TCGA, CGGA, and SangerBox, we focused on the relationship between CTHRC1 and tumorigenesis, progression, methylation, immunity, and prognosis. qPCR was used to detect CTHRC1 expression in glioma tissues and cell lines. Results The pan-cancer analysis showed that CTHRC1 was overexpressed in most tumors, and a significant correlation was observed between CTHRC1 expression and the prognosis of patients with cancer. CTHRC1 genetic alterations occur in diverse tumors and are associated with tumor progression. Levels of CTHRC1 promoter methylation were decreased in most cancer tissues compared with normal tissues. In addition, CTHRC1 coordinated the activity of ICP genes through diverse signal transduction pathways, was also associated with immune cell infiltration and the tumor microenvironment, and potentially represented a promising immunotherapy target. We identified CTHRC1-related genes across cancers using the GEPIA2 tool. The single-gene GO analysis of CTHRC1 across cancers showed that it was involved in some signaling pathways and biological processes, such as the Wnt signaling pathway, cell migration, and positive regulation of protein binding. The expression and function of CTHRC1 were also further verified in glioma tissues and cell lines. Conclusions CTHRC1 is overexpressed in various cancer types and functions as an important oncogene that may promote tumorigenesis and development through different mechanisms. CTHRC1 may represent an important therapeutic target for human cancers.


2001 ◽  
Vol 125 (7) ◽  
pp. 892-898 ◽  
Author(s):  
Andrey Korshunov ◽  
Andrey Golanov

Abstract Objective.—To evaluate a possible association between clinical outcome of patients with oligodendroglioma and expression of 2 cyclin-dependent kinase inhibitors, p21/Cip-1 (p21) and p27/Kip-1 (p27), and of DNA topoisomerase II-alpha (Ki-S1), which has been recently used as a marker of cellular proliferation. Design.—Ninety-one specially selected patients with cerebral oligodendrogliomas treated with surgery and radiotherapy were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p21, p27, and Ki-S1. A computerized color image analyzer was used to count immunostained nuclei. Results.—The mean Ki-S1 labeling index (LI) was found to be significantly prominent for World Health Organization (WHO) high-grade tumors (9.5% vs 3.2% for WHO low-grade tumors). In contrast, the mean p27 LI was significantly higher for low-grade tumors (43.3% vs 25.7% for high-grade tumors). The number of p21-positive cases and the mean p21 LI were found to be relatively equal for low- and high-grade tumors. For low-grade oligodendrogliomas, the progression-free and overall survival times were found to be significantly shorter for tumors with p27 LIs less than 20%. For high-grade oligodendrogliomas, survival times were significantly reduced for tumors with Ki-S1 LIs greater than 10%. Regression-tree analysis identified 4 groups of oligodendrogliomas with distinctly different outcomes: (1) 32 patients with low-grade tumors and p27 LIs greater than 20%; (2) 14 patients with low-grade tumors and p27 LIs less than 20%; (3) 25 patients with high-grade tumors and Ki-S1 LIs less than 10%; and (4) 20 patients with high-grade tumors and Ki-S1 LIs greater than 10%. Conclusions.—Immunoreactivity for Ki-S1 and p27 was found to be useful for further subdividing oligodendroglioma prognoses among low-grade and high-grade tumors. It seems unlikely that p21 immunohistochemistry will be of value for determining clinical outcomes for patients with oligodendrogliomas.


Pathobiology ◽  
2000 ◽  
Vol 68 (3) ◽  
pp. 137-143 ◽  
Author(s):  
Lydia Nakopoulou ◽  
Andreas C. Lazaris ◽  
Nikolaos Kavantzas ◽  
Paraskevi Alexandrou ◽  
Pauline Athanassiadou ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hang Xu ◽  
Xiaonan Zheng ◽  
Shiyu Zhang ◽  
Xianyanling Yi ◽  
Tianyi Zhang ◽  
...  

AbstractCurrent treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination.


2011 ◽  
Vol 363 (1-2) ◽  
pp. 301-307 ◽  
Author(s):  
Miroslav Vařecha ◽  
Michaela Potěšilová ◽  
Pavel Matula ◽  
Michal Kozubek

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