EZH2 Expression in Intestinal Neuroendocrine Tumors

Faviana, Pinuccia; Marconcini, Riccardo; Ricci, Sergio; Galli, Luca; Lippolis, Piero Vincenzo; Farci, Fabiola; Castagna, Maura; Boldrini, Laura

doi:10.1097/pai.0000000000000647

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…33 Overexpression of EZH2 in aggressive NET has been noted before in the lung and the gastrointestinal tract. 34,35 It will be important to study if pharmacologic inhibition of EZH2 can be used for the therapy of these highly malignant tumors. Sequencing of a limited gene panel revealed a single ATRX p.Q929E mutation in an NET G3 and an unexpected high frequency of NF1 mutations in both NET G3 and LCNEC.…”

Section: Discussionmentioning

confidence: 99%

Molecular Classification of Neuroendocrine Tumors of the Thymus

Dinter

Bohnenberger

Beck³

et al. 2019

Journal of Thoracic Oncology

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Introduction:The WHO classification of pulmonary neuroendocrine tumors (PNETs) is also used to classify thymic NETs (TNETs) into typical and atypical carcinoid (TC and AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), but little is known about the usability of alternative classification systems.Methods: One hundred seven TNET (22 TC, 51 AC, 28 LCNEC, and 6 SCC) from 103 patients were classified according to the WHO, the European Neuroendocrine Tumor Society, and a grading-related PNET classification. Low coverage whole-genome sequencing and immunohistochemical studies were performed in 63 cases. A copy number instability (CNI) score was applied to compare tumors. Eleven LCNEC were further analyzed using targeted next-generation sequencing. Morphologic classifications were tested against molecular features.Results: Whole-genome sequencing data fell into three clusters: CNI low , CNI int , and CNI high . CNI low and CNI int comprised not only TC and AC, but also six LCNECs. CNI high contained all SCC and nine LCNEC, but also three AC. No morphologic classification was able to predict the CNI cluster. Cases where primary tumors and metastases were available showed progression from low-grade to higher-grade histologies. Analysis of LCNEC revealed a subgroup of intermediate NET G3 tumors that differed from LCNEC by carcinoid morphology, expression of chromogranin, and negativity for enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2).Conclusions: TNETs fall into three molecular subgroups that are not reflected by the current WHO classification. Given the large overlap between TC and AC on the one hand, and AC and LCNEC on the other, we propose a

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Section: Discussionmentioning

confidence: 99%

Molecular Classification of Neuroendocrine Tumors of the Thymus

Dinter

Bohnenberger

Beck³

et al. 2019

Journal of Thoracic Oncology

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“…Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is involved in various biological processes (Comet 2016;Crea 2011). Increasing research has indicated that EZH2 is widely associated with carcinomas, such as hepatocellular carcinoma, colorectal cancer, melanoma and neuroendocrine tumors (Xiao 2019a;Di 2019;Emran 2019;Faviana 2019). Recently, a study showed that the epigenetic modifier EZH2 can suppress the expression of the immune checkpoint inhibitor PD-L1 by directly upregulating the level of the promoter H3K27me3 for CD274 and IRF1 in hepatoma cells and may serve as a potential therapeutic target for immunotherapy for treating immune-activated HCC (Xiao 2019b).…”

Section: Resultsmentioning

confidence: 99%

Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients

Wang

Zhou

et al. 2020

Mol Med

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Background Hepatocellular carcinoma (HCC) is a common malignant primary cancer with high mortality. Previous studies have demonstrated that RNA binding proteins (RBPs) are involved in the biological processes of cancers, including hepatocellular cancer. Methods In this study, we aimed to identify the clinical value of RNA-binding proteins for hepatocellular carcinoma. We obtained gene expression and clinical data of hepatocellular carcinoma patients from the TCGA and ICGC databases. The prognostic value of RBP-related genes in patients with hepatocellular carcinoma and their function were studied by comprehensive bioinformatics analyses. The gene signature of SMG5, EZH2, FBLL1, ZNF239, and IGF2BP3 was generated by univariate and multivariate Cox regression and LASSO regression analyses. We built and verified a prognostic nomogram based on RBP-related genes. The gene signature was validated by the ICGC database. The expression of RBP-related genes was validated by the Oncomine database, the Human Protein Atlas and Kaplan–Meier plotter. Result Most RBP-related genes were significantly different in cancer and normal tissues. The survival of patients in the different groups was significantly different. The gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters. Conclusion Gene signatures based on RNA-binding proteins can be independent risk factors for hepatocellular carcinoma patients.

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“…Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is involved in various biological processes (Crea, Hurt et al 2011, Comet, Riising et al 2016. More and more research has indicated that EZH2 is widely associated with carcinoma, such as hepatocellular carcinoma, colorectal cancer, melanoma and neuroendocrine tumors (Di, Weinan et al 2019, Emran, Chatterjee et al 2019, Faviana, Marconcini et al 2019. Recently, a study showed that the epigenetic modi cator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of CD274 and IRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC .…”

Section: Resultsmentioning

confidence: 99%

Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients

Wang

Zhou

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality among all human cancers. Studies have demonstrated that RNA binding proteins (RBPs) involved in the biological process of cancers including hepatocellular cancer. In this study, we aim to identify clinical value of RNA binding proteins for hepatocellular carcinoma.Methods: We analyses the data of HCC that downloaded from the Cancer Genome Atlas (TCGA) database and determined the differently expressed of RBPs between cancer and normal tissues. We further elucidate the function of RBPs by utilized Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene signature of SMG5, EZH2, FBLL1, ZNF239, IGF2BP3 were generated by performed the univariate and multivariate Cox regression and LASSO regression analysis. CIBERSORT analysis was used to evaluation of tumor-infiltrating immune cells in different group. We built and verify a prognosis nomogram base on RBPs-related genes. Gene signature was validated by the International Cancer Genome Consortium (ICGC) database. The expressions of RBPs-related genes were validated by using Oncomine database, and the Human Protein Atlas.Result: Most of RBPs-related genes were significantly different in cancer and normal tissue. The survival of patients in the different group was statistically different. The Gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters (AUC=0.758). The patients in the high-risk group were more likely to have a higher Macrophages M0. Conclusion: Gene signature constructed by RNA binding proteins can be independent risk factors for hepatocellular carcinoma patients.

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EZH2 Expression in Intestinal Neuroendocrine Tumors

Cited by 9 publications

References 24 publications

Molecular Classification of Neuroendocrine Tumors of the Thymus

Molecular Classification of Neuroendocrine Tumors of the Thymus

Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients

Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients

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