Elevated TOP2A and UBE2C expressions correlate with poor prognosis in patients with surgically resected lung adenocarcinoma: a study based on immunohistochemical analysis and bioinformatics

Guo, Wei; Sun, Sijin; Guo, Lei; Song, Peng; Xue, Xuemin; Zhang, Hao; Zhang, Guochao; Wang, Zhen; Qiu, Bin; Tan, Fengwei; Xue, Qi; Gao, Yibo; Gao, Shugeng

doi:10.1007/s00432-020-03147-4

Cited by 25 publications

(19 citation statements)

References 53 publications

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“…TOP2A gene can encode one DNA topoisomerase responsible for controlling and altering DNA topology in the process of transcription [ 14 ]. In addition, TOP2A expressions in different cancers are suggested as the favorable prognostic biomarker that predict cancer progression and relapse, and it also serves as the risk factor for dismal survival [ 15–18 ]. In HCC, TOP2A has been shown to be upregulated in multiple studies.…”

Section: Discussionmentioning

confidence: 99%

Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression

et al. 2021

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Type IIA topoisomerase (TOP2A) is upregulated in hepatocellular carcinoma (HCC) and its expression is positively correlated with poor prognosis. However, the underlying molecular mechanism of this connection are poorly understood. Hence, the present work aimed to examine the possible mechanisms which may be useful in identifying a potential therapeutic strategy. The differential expression of TOP2A mRNA in HCC as compared with adjacent normal tissue was analyzed using the Oncomine database. The expression levels of TOP2A in HCC specimens and cell lines were assessed by Western blot and RT-qPCR. Stable cell lines were generated to knockdown or overexpress TOP2A, and then cell growth, migration, and invasion were analyzed. Furthermore, this study examined epithelial-mesenchymal transition (EMT) as well as the activation of related pathways. Additionally, the correlation between TOP2A levels and E-cadherin/Snail expression was determined in 72 HCC specimens. Higher expression levels of TOP2A were observed in HCC in Oncomine datasets, and the results were verified using 40 pairs of HCC specimens and peritumoral tissues. TOP2A expression levels were remarkably elevated in cells with great metastatic capacity. In addition, HCC cell growth, migration, and invasion were suppressed after TOP2A knockdown in MHCC97H cells (MHCC97H-shRNA-TOP2A), while these capabilities were promoted in TOP2A-overexpressing Hep3B cells (Hep3B-TOP2A). Furthermore, EMT was inhibited in MHCC97H-shRNA-TOP2A cells, but induced in Hep3B-TOP2A cells. The induction of EMT by TOP2A was shown to be mediated by Snail, as TOP2A promoted Snail expression through the p-ERK1/2/p-SMAD2 signaling pathway. TOP2A level showed a negative correlation with E-cadherin, whereas a positive correlation with that of vimentin and Snail in human HCC specimens by immunohistochemistry analyses. Kaplan–Meier survival curves revealed that TOP2A upregulation showed a positive correlation with poor prognosis patients. Taken together, TOP2A possibly enhances the metastasis of HCC by promoting EMT through the mediation of the p-ERK1/2/p-SMAD2/Snail pathway. This indicates that TOP2A maybe a potential factor to predict the prognosis of HCC.

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Section: Discussionmentioning

confidence: 99%

Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression

et al. 2021

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“…As for pathological stage, Chen et al (27) also reported the similar finding previously. A recent study identified TOP2A as a negative prognostic factor in LUAD (28), but the prognostic value of TOP2A in LUSC remains obscure. STK11 is a frequently mutated gene and has been identified as an important suppressor in LUSC (29).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma

et al. 2020

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BackgroundThis study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.MethodsWe retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.ResultsOf 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.ConclusionsSignificant differences exist among three subtypes of LUSC in molecular characterizations.

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“…TOP2A has been reported in the upregulation of various malignant tumors, including LUAD. For instance, Guo et al [39] found that TOP2A overexpression was correlated with poor prognosis of LUAD patients. Wang et al [40] revealed that the higher the CCNB1 expression level, the lower the OS rate and disease-free survival rate in LC patients.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Significance and Potential Molecular Mechanisms of Synaptojanin 2 in Lung Adenocarcinoma

Chen

et al. 2020

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Background Lung adenocarcinoma (LUAD) is the main pathological type of pulmonary malignant tumors. Synaptojanin 2 (SYNJ2), a member of the synaptojanin family, is considered as an attractive underlying therapeutic target in several types of cancer. The purpose of the current research was to comprehensively investigate the molecular function and underlying mechanism of SYNJ2 in LUAD with the goal of providing a promising therapeutic target for LUAD. Methods We applied tissue microarrays, immunohistochemistry (IHC), high-throughput RNA sequencing (RNA-seq) data, and gene microarrays of public databases to comprehensively examine the protein level, mRNA expression, clinical significance, and prognosis value of SYNJ2 in LUAD. The standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were computed to evaluate the comprehensive expression value of SYNJ2 in LUAD. Kaplan-Meier survival curves were plotted to determine the overall survival of SYNJ2 with different expression levels in LUAD. Univariate and multivariate cox regression analyses were implemented to investigate the dependent prognostic ability of SYNJ2 expression and the clinically-relevant traits of LUAD. Moreover, SYNJ2 co-expressed genes were screened for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) function analysis and protein–protein interactions (PPI) network construction. Results SYNJ2 overexpression in LUAD was confirmed by 2,299 LUAD samples and 1,387 non-tumor tissues obtained from tissue microarrays along with TCGA and public gene microarrays. The pooled SMD was 1.29 (95% CI: 1.09-1.48, I-square=78.6%, P<0.001) and the area under the curve (AUC) of the SROC was 0.88 (95%CI: 0.85-0.91). Compared to the upregulation of SYNJ2, SYNJ2 downregulation could improve OS in LUAD patients to some extent. SYNJ2 may facilitate the proliferation and progression of LUAD by modulating the cell cycle and TGF-beta signaling pathways. The 10 SYNJ2 co-expressed key genes selected from PPI network were all prominently implicated with the prognosis of LUAD patients. Conclusion SYNJ2 may contribute as an attractive and prospective therapeutic target in LUAD.

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Elevated TOP2A and UBE2C expressions correlate with poor prognosis in patients with surgically resected lung adenocarcinoma: a study based on immunohistochemical analysis and bioinformatics

Cited by 25 publications

References 53 publications

Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression

Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression

Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma

The Clinical Significance and Potential Molecular Mechanisms of Synaptojanin 2 in Lung Adenocarcinoma

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