Prognostic Value and Significant Pathway Exploration Associated with TOP2A Involved in Papillary Thyroid Cancer

Abstract

Background: Topoisomerase 2-alpha (TOP2A) has been identified as a hub gene that played an important role in the initiation and progression of thyroid carcinoma (THCA). However, the exact function of TOP2A in papillary thyroid cancer (PTC) remained elusive. The current study aimed to evaluate the TOP2A expression, prognosis significance and key signaling pathways involved in PTC. Methods: We firstly evaluated the expression of TOP2A in PTC via UALCAN, cBioportal, HPA and LinkdedOmics databases. Genetic alteration of TOP2A in PTC was then explored in cBioportal. Prognostic impacts of TOP2A expression on disease-free survival (DFS) of PTC patients were subsequently evaluated using Kaplan-Meier plotter and Gepia databases. Taking gender, age, cancer stage, T, N and M stages into consideration, we compared survival difference between TOP2A high and low expression groups. KEGG pathway analysis in WebGestalt and GSEA analysis were further performed to reveal the potential TOP2A-associated signaling pathways involved in PTC. Finally, the upstream microRNAs of TOP2A were assessed using DIANA, TargetScan, miRDB and miRWALK database, followed by mechanism exploration of upstream microRNAs. Results: 1) The mRNA and protein of TOP2A were highly expressed in PTC tissue compared with normal thyroid tissue. TOP2A expression was associated with patient's age, N stage and cancer stage (all P<0.05). TOP2A protein was mainly localized to nucleoplasm. 2) Most of samples occurred the missense substitution, and mutation site was located at K1199E. Nucleotide mutations were mainly presented as G>A (35.29%). 3) TOP2A high expression significantly influenced the DFS of PTC patients (P=0.015). Restricted survival analysis showed that TOP2A high expression caused poorer DFS of female patients (P=0.003) and those with age <60 years old (P=0.002), early clinical stage (P=0.012), N0 stage (P=0.002) or M0 stage (P=0.040). 4) Pathway analysis suggested that TOP2A positively participated in the cell cycle, oocyte meiosis and p53 signaling pathways (all P<0.05) involved in thyroid cancer. Conclusion:The expression of TOP2A was higher in PTC tissue, which resulted in a worse DFS of patients with PTC. TOP2A might act as an effective therapeutic target for PTC treatment.

TOP2A expression in pheochromocytoma and abdominal paraganglioma: a novel marker of poor clinical outcome?

“…TOP2A has been suggested as a marker of poor prognosis and a potential therapeutic marker in several other cancer types, which make a similar mechanism in PPGL plausible. Similarly to the results presented in this study, Gong et al [24] showed the potential role of TOP2A as a prognostic and therapeutic marker in papillary thyroid cancer as well as Chen et al [25] did in renal cell carcinoma. Like Cluster 1 mutations in PPGL, hypoxia inducible factor (HIF) alterations due to VHL gene mutations are found in renal cell carcinoma, suggesting a potential similar molecular mechanism in PPGL.…”

Integrative bioinformatics analysis of miRNA and mRNA expression profiles identified some potential biomarkers for breast cancer

“…Mou-chun Gong et al found that TOP2A is a target for two microRNAs including miR-96-5p and miR-635. Based on previous study, miR96-5p signi cantly upregulated in papillary thyroid cancer (PTC) (35). miR-96-5p has a tumor-promoting role in breast cancer.…”

Integrative bioinformatics analysis of miRNA and mRNA expression profiles identified some potential biomarkers for breast cancer

“…Mouchun Gong et al found that TOP2A is a target for two microRNAs including miR-96-5p and miR-635. Based on the previous study, miR96-5p significantly upregulated in papillary thyroid cancer (PTC) [35]. miR-96-5p has a tumor-promoting role in breast cancer.…”