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Gene Signature Associated with Upregulation of the Wnt/?-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.

ABSTRACT: PURPOSE:To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization. MATERIALS AND METHODS:This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar-cell carcinoma. Disease, procedure data, and tumor response data were collected. Dimensionality reduction was performed by using principal component analysis. A linear support vector machine was used to learn a prediction rule and identify the genes most predictive of objective tumor response (partial or complete) per modified Response Evaluation Criteria In Solid Tumors. Cross-validation was used to test the prediction on the holdout set. Permutation testing was used to determine statistical significance of prediction accuracy. Recursive feature elimination was used to identify the most predictive genes. RESULTS:At 4 months after embolization, 9 tumors showed a response and 8 did not. Using the top two principal components, prediction accuracy of the gene mutation signature was 70% (±11%), which was statistically significant (P < .05). The most predictive genes were CTNNB1, MEN1, and NCOR1: three genes associated with the Wnt/?-catenin and hypoxia signaling pathways. CONCLUSIONS:This study identifies gene mutations in tumors treated with transarterial embolization. A gene-mutation signature obtained from the mutation data suggests that upregulation of the Wnt/?-catenin signaling pathway may be associated with sensitivity to embolization.

SUBMITTER: Ziv E

PROVIDER: S-EPMC5325772 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.

Ziv Etay E Yarmohammadi Hooman H Boas F Edward FE Petre Elena Nadia EN Brown Karen T KT Solomon Stephen B SB Solit David D Reidy Diane D Erinjeri Joseph P JP

Journal of vascular and interventional radiology : JVIR 20170124 3

<h4>Purpose</h4>To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization.<h4>Materials and methods</h4>This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, mel ...[more]

PMID: 28126478

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Project description:ObjectiveThis study aimed to establish a prognostic model related to prostate cancer (PCa) recurrence-free survival (RFS) and identify biomarkers.MethodsThe RFS prognostic model and key genes associated with PCa were established using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression from the Cancer Genome Atlas (TCGA)-PRAD and the Gene Expression Omnibus (GEO) GSE46602 datasets. The weighted gene co-expression network (WGCNA) was used to analyze the obtained key modules and genes, and gene set enrichment analysis (GSEA) was performed. The phenotype and mechanism were verified in vitro.ResultsA total of 18 genes were obtained by LASSO regression, and an RFS model was established and verified (TCGA, AUC: 0.774; GSE70768, AUC: 0.759). Three key genes were obtained using multivariate Cox regression. WGCNA analysis obtained the blue module closely related to the Gleason score (cor = -0.22, P = 3.3e - 05) and the unique gene glutathione peroxidase 2 (GPX2). Immunohistochemical analysis showed that the expression of GPX2 was significantly higher in patients with PCa than in patients with benign prostatic hyperplasia (P < 0.05), but there was no significant correlation with the Gleason score (GSE46602 and GSE6919 verified), which was also verified in the GSE46602 and GSE6919 datasets. The GSEA results showed that GPX2 expression was mainly related to the epithelial-mesenchymal transition (EMT) and Wnt pathways. Additionally, GPX2 expression significantly correlated with eight kinds of immune cells. In human PCa cell lines LNCaP and 22RV1, si-GPX2 inhibited proliferation and invasion, and induced apoptosis when compared with si-NC. The protein expression of Wnt3a, glycogen synthase kinase 3β (GSK3β), phosphorylated (p)-GSK3β, β-catenin, p-β-catenin, c-myc, cyclin D1, and vimentin decreased; the expression of E-cadherin increased; and the results for over-GPX2 were opposite to those for over-NC. The protein expression of GPX2 decreased, and β-catenin was unchanged in the si-GPX2+ SKL2001 group compared with the si-NC group.ConclusionWe successfully constructed the PCa RFS prognostic model, obtained RFS-related biomarker GPX2, and found that GPX2 regulated PCa progression and triggered Wnt/β-catenin/EMT pathway molecular changes.

Dataset Information

Gene Signature Associated with Upregulation of the Wnt/?-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.

Publications

Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.

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