Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

Hou, Guoxin; Li, Panpan; Yang, Jing; Wen, Shulin

doi:10.1371/journal.pone.0174515

Cited by 173 publications

(148 citation statements)

References 64 publications

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“…Through an Oncomine Research Premium edition upgrade, downloaded raw datasets that included mRNA expression, clinical and pathological information, and survival data (Thermo Fisher, Ann Arbor, MI; http://www.oncomine.org). A Kaplan‐Meier plotter (http://www.kmplot.com) was used to confirm the prognostic significance of the HSP90B1 mRNA expression in lung cancers . The desired Affymetrix ID of the HSP90B1 gene was 200599_s_at.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells

Duan

Xin

2020

Thoracic Cancer

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Background Endoplasmic reticulum stress exists within a tumor. Glucose‐regulated protein 94 (GRP94) is a stress‐induced chaperone protein involved in tumor development and progression. Its role in myeloma, colon cancer, and other tumors has been confirmed, but its role in lung cancer is unclear. This study aimed to determine the role of GRP94 in lung cancer progression and prognostic prediction. Methods Immunohistochemical staining of GRP94 in human lung adenocarcinoma (AD) and corresponding normal tissue was performed, and its relationship with FOXP3+ regulatory T‐cell (Treg) infiltration analyzed. We investigated the role of GRP94 in the behavior of lung AD cells by inhibiting GRP94 expression in A549 cells. Western blotting was used to detect the TGF‐β/SMAD2 signaling molecules and explore the possible molecular mechanism of GRP94. Results GRP94 mRNA (encoded by HSP90B1) and protein levels were upregulated and elevated, respectively, in lung AD compared to normal lung tissues. High GRP94 expression was associated with an advanced disease stage and poor survival. There was a positive correlation between GRP94 expression and FOXP3+ Treg infiltration into lung AD tissues. Our results confirm that GRP94 knockdown inhibits cell proliferation and promotes cell apoptosis by increasing caspase‐7 and CHOP levels in lung AD cells. TGF‐β and SMAD2 protein levels were decreased after GRP94 depletion. Conclusions Our study revealed that that GRP94 expression in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of GRP94 may involve inducing Treg infiltration by promoting the TGF‐β signaling pathway. Key points GRP94 protein levels were elevated in lung AD tissues compared to normal lung tissues. The high expression of GRP94 in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of the molecule GRP94 may involve the stimulation of Treg infiltration via promotion of the TGF‐β signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells

Duan

Xin

2020

Thoracic Cancer

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“…The Oncomine gene expression array database (https://www.oncomine.org) was used to assess the HN1 mRNA expression levels in HCC datasets. In this study, the differential mRNA expression of HN1 between HCC and normal liver tissues was compared using a Student's t ‐test …”

Section: Methodsmentioning

confidence: 99%

“…In the present study, Kaplan‐Meier Plotter was used to evaluate the overall survival (OS), relapse‐free survival (RFS), progression‐free survival (PFS), and disease‐specific survival (DSS) of HCC patients. Individuals were separated into two groups based on median gene expression; high (≥median expression) and low expression (<median expression) …”

Section: Methodsmentioning

confidence: 99%

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Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met

Chen

Sun

Mao

et al. 2019

The Kaohsiung J of Med Scie

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Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse‐free survival, progression‐ free survival and disease‐specific survival in HCC patients via exploring the Kaplan‐Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over‐expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c‐Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c‐Met; consistently, HN1 over‐expression reversed these effects. Meanwhile, down‐regulation of c‐Met partly eliminated the effect of HN1 over‐expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up‐regulating the expression of c‐Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC.

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“…PCLAF encodes a PCNA-binding protein and is a regulator of DNA repair during DNA replication. In addition, TOP2A (DNA Topoisomerase II Alpha; Huang, Liu, Meng, & Niu, 2015;Hou, Liu, Yang, & Wen, 2017), CDC20 (Cell Division Cycle 20; Kato et al, 2012a;Z. Figure 2 shows the subnetwork of PCLAF, where the red nodes indicate the probe of PCLAF.…”

Section: Nsclc Datamentioning

confidence: 99%

Robust network‐based regularization and variable selection for high‐dimensional genomic data in cancer prognosis

Ren

et al. 2019

Genetic Epidemiology

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In cancer genomic studies, an important objective is to identify prognostic markers associated with patients' survival. Network‐based regularization has achieved success in variable selections for high‐dimensional cancer genomic data, because of its ability to incorporate the correlations among genomic features. However, as survival time data usually follow skewed distributions, and are contaminated by outliers, network‐constrained regularization that does not take the robustness into account leads to false identifications of network structure and biased estimation of patients' survival. In this study, we develop a novel robust network‐based variable selection method under the accelerated failure time model. Extensive simulation studies show the advantage of the proposed method over the alternative methods. Two case studies of lung cancer datasets with high‐dimensional gene expression measurements demonstrate that the proposed approach has identified markers with important implications.

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Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

Cited by 173 publications

References 64 publications

Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells

Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells

Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met

Robust network‐based regularization and variable selection for high‐dimensional genomic data in cancer prognosis

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