Dataset Information

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma.

ABSTRACT:

Background

Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment.

Methods

Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n?=?1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language.

Findings

HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEM^high tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEM^low tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment.

Interpretation

Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM.

SUBMITTER: Han MZ

PROVIDER: S-EPMC6557785 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma.

Han Ming-Zhi MZ Wang Shuai S Zhao Wen-Bo WB Ni Shi-Lei SL Yang Ning N Kong Yang Y Huang Bin B Chen An-Jing AJ Li Xin-Gang XG Wang Jian J Wang Dong-Hai DH

EBioMedicine 20190412

<h4>Background</h4>Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment.<h4>Methods</h4>Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. ...[more]

PMID: 30987862

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Project description:BACKGROUND: LATS2, which encodes a novel serine/threonine kinase, is known to be important in centrosome duplication and in the maintenance of genomic stability. Recently, a potential role for LATS2 in cancer has been reported. In breast cancer and acute lymphoblastic leukemia (ALL), LATS2 mRNA is downregulated and has been suggested to be a tumor suppressor. However, the role of LATS2 in nasopharyngeal carcinoma has not been investigated. In this study, we aimed to investigate the expression pattern of LATS2 and its clinicopathological involvement in nasopharyngeal carcinoma to understand its effect on cell survival. METHODS: Using quantitative real time PCR and immunoblotting, the expression of LATS2 was detected in nasopharyngeal carcinoma cell lines and in the immortalized nasopharyngeal epithelial cell line NP69. Using immunohistochemistry, we analyzed LATS2 protein expression in 220 nasopharyngeal carcinoma cases. The association of LATS2 protein expression with the clinicopathological characteristics and the prognosis of nasopharyngeal carcinoma were subsequently assessed. Using methylation specific PCR, we detected the methylation status of the LATS2 promoter. RNA interference was performed by transfecting siRNA to specifically knock down LATS2 expression in 5-8F and CNE2. RESULTS: LATS2 protein was detected in 178 of 220 (80.91%) cases of nasopharyngeal carcinoma. LATS2 overexpression was a significant, independent prognosis predictor (P = 0.037) in nasopharyngeal carcinoma patients. Methylation specific PCR revealed that 36.7% (11/30) of nasopharyngeal carcinoma tissues and all of the chronic nasopharyngeal inflammation samples were methylated. Functional studies showed that the suppression of LATS2 expression in nasopharyngeal carcinoma (5-8F and CNE2) cell lines by using specific small interfering (siRNA) resulted in the inhibition of growth, induction of apoptosis and S-phase cell cycle increase. Overexpression of LATS2 in NP69 stimulated cell proliferation. CONCLUSIONS: Our results indicate that LATS2 might play a role in the tumorigenesis of nasopharyngeal carcinoma by promoting the growth of nasopharyngeal carcinoma cells. Transfection with specific siRNA might be feasible for the inhibition of growth, induction of apoptosis and S phase increase in nasopharyngeal carcinoma.

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Dataset Information

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma.

Background

Methods

Findings

Interpretation

Publications

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma.

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