Expression Analysis of Immune Modulatory Molecules HLA-E and HLA-F in 69 Cases of Glioblastoma: An Association with Survival

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F20%3A00072795" target="_blank" >RIV/65269705:_____/20:00072795 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41379-020-0481-8" target="_blank" >https://www.nature.com/articles/s41379-020-0481-8</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Expression Analysis of Immune Modulatory Molecules HLA-E and HLA-F in 69 Cases of Glioblastoma: An Association with Survival

Popis výsledku v původním jazyce

Background: Glioblastoma (GB) is considered to be one of the deadliest human cancers, which responds poorly to both traditional and experimental therapeutic approaches, stubbornly persisting with a dismal survival of about 12-15 months from diagnosis. Central nervous system has been traditionally considered an immunologically privileged site; GB appears to benefit from this immunosuppressive milieu. Human leukocyte antigens E and F (HLA-E, HLA-F) are nonclassical HLA class I molecules well known to be involved in the protection of semi- allogeneic fetal allografts from the maternal immune system, and in transplant tolerance and viral and tumoral immune escape. The role of HLA-G and HLA-E expression in GBM is not well characterized. Design: We performed qRT PCR analyses of the HLA-E and HLA-F expressions in 69 GB tissue samples and 21 non-tumor brain tissues (obtained from resections from drug-resistant epilepsy patients). GB patients underwent standard therapeutic protocol including surgical resection followed by the concomitant chemoradiotherapy with temozolomide. Total RNA from all tumor and brain non-tumor tissue specimens was extracted and further analyzed using specific TaqMan Gene Expression Assays (ThermoFisher Scientific). MGMT methylation status as well as IDH1 mutation status were evaluated in all GBs. Results: Statistical analysis revealed that both HLA-E and HLA-F are significantly upregulated in GB samples in comparison with nontumorbrain tissues (Fold Change (FC) = 2.05, p &lt; 0.001; and FC = 2.02, p = 0.001, respectively; Mann Whitney analysis). Contraintuitively, subsequent survival analyses showed significant (p = 0.01; Kaplan-Meier analysis) association between low expression of HLA-E and shorter overall survival (OS) of GB patients (median OS = 8.9 months vs. 13.5 months in patients with high HLA-E expression). Similar but not significant association has been observed also in HLA-F (p = 0.16). Finally, we showed that ionizing radiation (RT) increased both HLAE and HLA-F expressions in GB cells in vitro in dose and time dependent manners. Conclusions: We described deregulated expressions of HLA-E and HLA-F in GBM tissue in comparison with non-tumor brain tissue and showed that HLA-E could be a promising prognostic molecule in GBM patients; and suggested that nonclassical HLA class I molecules are affected by RT.

Název v anglickém jazyce

Expression Analysis of Immune Modulatory Molecules HLA-E and HLA-F in 69 Cases of Glioblastoma: An Association with Survival

Popis výsledku anglicky

Background: Glioblastoma (GB) is considered to be one of the deadliest human cancers, which responds poorly to both traditional and experimental therapeutic approaches, stubbornly persisting with a dismal survival of about 12-15 months from diagnosis. Central nervous system has been traditionally considered an immunologically privileged site; GB appears to benefit from this immunosuppressive milieu. Human leukocyte antigens E and F (HLA-E, HLA-F) are nonclassical HLA class I molecules well known to be involved in the protection of semi- allogeneic fetal allografts from the maternal immune system, and in transplant tolerance and viral and tumoral immune escape. The role of HLA-G and HLA-E expression in GBM is not well characterized. Design: We performed qRT PCR analyses of the HLA-E and HLA-F expressions in 69 GB tissue samples and 21 non-tumor brain tissues (obtained from resections from drug-resistant epilepsy patients). GB patients underwent standard therapeutic protocol including surgical resection followed by the concomitant chemoradiotherapy with temozolomide. Total RNA from all tumor and brain non-tumor tissue specimens was extracted and further analyzed using specific TaqMan Gene Expression Assays (ThermoFisher Scientific). MGMT methylation status as well as IDH1 mutation status were evaluated in all GBs. Results: Statistical analysis revealed that both HLA-E and HLA-F are significantly upregulated in GB samples in comparison with nontumorbrain tissues (Fold Change (FC) = 2.05, p &lt; 0.001; and FC = 2.02, p = 0.001, respectively; Mann Whitney analysis). Contraintuitively, subsequent survival analyses showed significant (p = 0.01; Kaplan-Meier analysis) association between low expression of HLA-E and shorter overall survival (OS) of GB patients (median OS = 8.9 months vs. 13.5 months in patients with high HLA-E expression). Similar but not significant association has been observed also in HLA-F (p = 0.16). Finally, we showed that ionizing radiation (RT) increased both HLAE and HLA-F expressions in GB cells in vitro in dose and time dependent manners. Conclusions: We described deregulated expressions of HLA-E and HLA-F in GBM tissue in comparison with non-tumor brain tissue and showed that HLA-E could be a promising prognostic molecule in GBM patients; and suggested that nonclassical HLA class I molecules are affected by RT.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30109 - Pathology

Projekt

<a href="/cs/project/NV17-32758A" target="_blank" >NV17-32758A: Imunopatologické mechanismy geneze, průběhu a léčebné odpovědi glioblastomu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů