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.
The CMOS variable gain low noise amplifier (LNA) presented in this paper is designed for frequency band 4.2 -4.8 GHz ultra-wideband (UWB) application specified in China. Wideband input matching with low noise performance codesign method is shown. A three-bit digital programmable gain control circuit is exploited to achieve variable gain. Fabricated with 0.13-ȝm RF CMOS process, the die size with ESD-pads is 0.9 mm 2 . Drawn 18 mA from 1.2 V DC supply, the LNA exhibits 2.3 dB minimum noise figure, S(1,1) less than -9 dB and S(2,2) less than -10 dB. Maximum and minimum power gain are 28 dB and 16 dB respectively, about 4 dB/step with four gain modes in all. Input 1dB compression point is -10 dBm and input third order intercept point (IIP3) is -2 dBm.
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