Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype

Li, Hao-Ran; Qiu, Bai‐Quan; Gao, Jian; Chun, Jennifer; Jiang, Jiahao; Ding, Jianyong

doi:10.1136/jclinpath-2019-205778

Cited by 10 publications

(15 citation statements)

References 22 publications

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“…We performed a meta-analysis to confirm low SETBP1 expression in GC based on the GEO database ( Figure 2B ), finding the TCGA and GEO results to be consistent. Furthermore, we showed that SETBP1 expression in GC cell lines (HGC-27, MGC-803, AGS, and MKN-28) was significantly lower than that in the GES-1 cell line ( Figure 2A ), consistent with earlier studies ( 5 , 27 ). Therefore, the findings of this study indicate that SETBP1 may act as a tumor suppressor gene.…”

Section: Discussionsupporting

confidence: 91%

“…SETBP1 expression has been extensively studied in various diseases, including cancers, where it is abnormal compared with normal tissues. These studies have involved several cancer types, including non-small cell lung cancer ( 5 ), hematologic malignancies ( 26 ), colorectal cancer ( 27 ), ovarian cancer ( 14 ), breast cancer ( 12 ), and gastric cancer ( 28 , 29 ). However, SETBP1 appears to play a dual role in different cancer types.…”

Section: Discussionmentioning

confidence: 99%

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The Role of SETBP1 in Gastric Cancer: Friend or Foe

Fang

Liu

et al. 2022

Front. Oncol.

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BackgroundGastric cancer (GC) remains a common disease with a poor prognosis worldwide. The SET binding protein 1 (SETBP1) has been implicated in the pathogenesis of several cancers and plays a dual role as an oncogene and a tumor suppressor gene. However, the role and underlying mechanism of SETBP1 in GC remain unclear.Materials and MethodsWe used next-generation RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to explore the correlation between SETBP1 expression and tumor progression. We then quantified SETBP1 expression in GC cells with real-time quantitative polymerase chain reactions (RT-qPCR). The chi-square test and logistic regression were used to assess the correlation between SETBP1 expression and clinicopathological features. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the relationship between SETBP1 expression and survival. Finally, gene set enrichment analyses (GSEA) were used to examine GC-related signaling pathways in low and high SETBP1 expressing samples.ResultsWe found SETBP1 expression levels in GC tissues to be significantly lower than in adjacent non-tumor tissues in the TCGA database. In addition, SETBP1 expression differed significantly between groups classified by tumor differentiation. Furthermore, SETBP1 expression in diffuse-type GC was significantly higher than in intestinal-type GC. However, it did not differ significantly across pathological- or T-stage groups. RT-qPCR and comprehensive meta-analysis showed that SETBP1 expression is downregulated in GC cells and tissues. Interestingly, SETBP1 expression in poorly- or un-differentiated GC cells was higher than in well-differentiated GC cells. Moreover, the chi-square test and logistic regression analyses showed that SETBP1 expression correlates significantly with tumor differentiation. Kaplan–Meier curves indicated that patients with relatively high SETBP1 expression had a poor prognosis. Multivariate analyses indicated that SETBP1 expression might be an important predictor of poor overall survival in GC patients. GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression.ConclusionSETBP1 may play a dual role in GC progression.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The Role of SETBP1 in Gastric Cancer: Friend or Foe

Fang

Liu

et al. 2022

Front. Oncol.

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“…The results of Weber et al showed that an enhanced expression level of HEYL decreased cancer cell dissemination and the absolute number of metastases formed, while the capacity of cell metastasis remained good, indicating that HEYL can function as a negative regulator by inhibiting the infiltration of metastasis-initiating cells ( Weber et al, 2019 ). At the same time, we found two other tumor suppression genes, SETBP1 and SULF1 ( Lai et al, 2008 ; Li et al, 2020 ). It was reported that decreased expression of SETBP1 contributed to the development of non-small-cell lung cancer cells by increasing tumor cell proliferation, migration, and invasion and was associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 57%

Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients

Liang

2022

Front. Cell Dev. Biol.

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The clinical outcome of heterogeneous bladder cancer (BCa) is impacted by varying molecular characteristics and clinical features, and new molecular classification is necessary to recognize patients with dichotomized prognosis. We enrolled a total of 568 BCa patients from the TCGA-BLCA and GSE13507 cohorts. A total of 107 candidate genes, which were mostly involved in the extracellular matrix-associated pathway, were first selected through the consensus value of the area under the receiver operating characteristic curve (AUC). Furthermore, absolute shrinkage and selection operation regression analysis was implemented to reveal the 15 genes and establish the prognostic signature. The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731). Multivariate Cox analysis involving the signature and clinical features indicated that the signature is an independent factor for the prediction of BCa prognosis. We also explored potential targeted therapy for BCa patients with high- or low-risk scores and found that patients with high risk were more suitable for chemotherapy with gemcitabine, doxorubicin, cisplatin, paclitaxel, and vinblastine (all p < 0.05), but anti-PD-L1 therapy was useless. We knocked down HEYL with siRNAs in T24 and 5,637 cells, and observed the decreased protein level of HEYL, and inhibited cell viability and cell invasion. In summary, we proposed and validated a 15-top-prognostic gene-based signature to indicate the dichotomized prognosis and response to targeted therapy.

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“…TCF4, as an important regulator of epithelial-mesenchymal transition and downstream of the Wnt/β-catenin signaling pathway, has been reported to be involved in cancer metastasis [ 46 ]. SET binding protein 1 (SETBP1), known as PP2A phosphatase activity inhibitor, was implicated in cancer pathogenesis such as leukemic malignancies [ 47 ], colorectal cancer [ 48 ], lung cancer [ 49 ], and breast cancer [ 50 ]. Under-expression of SETBP1 promoted the proliferation and invasion of NSCLC cells through activating the ERK1/2 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

et al. 2022

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Background Bladder cancer (BLCA) is a malignant tumor with a dismay outcome. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. Therefore, we aimed to explore the function and prognostic value of CRs in BLCA patients. Methods Chromatin regulators (CRs) were acquired from the previous top research. The mRNA expression and clinical information were downloaded from TCGA and GEO datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to select the prognostic gene and construct the risk model for predicting outcome in BLCA. The Kaplan-Meier analysis was used to assess the prognosis between high- and low-risk groups. We also investigated the drug sensitivity difference between high- and low-risk groups. CMAP dataset was performed to screen the small molecule drugs for treatment. Results We successfully constructed and validated an 11 CRs-based model for predicting the prognosis of patients with BLCA. Moreover, we also found 11 CRs-based model was an independent prognostic factor. Functional analysis suggested that CRs were mainly enriched in cancer-related signaling pathways. The CR-based model was also correlated with immune cells infiltration and immune checkpoint. Patients in the high-risk group were more sensitive to several drugs, such as mitomycin C, gemcitabine, cisplatin. Eight small molecule drugs could be beneficial to treatment for BLCA patients. Conclusion: In conclusion, our study provided novel insights into the function of CRs in BLCA. We identified a reliable prognostic biomarker for the survival of patients with BLCA.

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Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype

Cited by 10 publications

References 22 publications

The Role of SETBP1 in Gastric Cancer: Friend or Foe

The Role of SETBP1 in Gastric Cancer: Friend or Foe

Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

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