Novel approach for analyzing NF-kB pathway activity in primary CNS lymphoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16565
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yokohama City University
• Principal Investigator: Nakamura Taishi 横浜市立大学, 附属市民総合医療センター, 助教 (60771615)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 中枢神経原発悪性リンパ腫 / DNAメチル化 / NF-kB pathway / リン酸化p65

Outline of Final Research Achievements

In this project, we obtained primary CNS lymphoma (PCNSL) tumors and the patients’ clinical data. We found out a key subdomain of p65 in constitutive NF-kB pathway activation using established PCNSL cell-line. We focused on phosphorated p65 distribution and expression level in PCNSL tissues. We combined genome-wide methylation data, multiple mutation status and analyzed correlation between these molecular status and clinical prognosis. Though resulted in no clinical impact of phosphorated p65 distribution and expression level to PCNSL patient prognosis in the primary analysis, the phosphorated p65 were activated in infiltrating zone in the tumor. So we are conducting additional analysis to find out clinical impact of it.

Free Research Field

悪性脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

PCNSLにおいてNF-kB pathwayが腫瘍において恒常的に活性化し,なかでもcanonical pathwayに依存している結果を得た上でそのサブドメインであるp65のリン酸化状態の発現が核内移行し標的遺伝子を活性化させることを明らかにした。集積した症例についてNF-kB pathwayの恒常的活性化及びリン酸化p65の発現がPCNSLの予後を規定していないことが示された。一方で、壊死や腫瘍境界部分での活性は腫瘍の浸潤性と関与しておりより詳細な発現評価が臨床においてもインパクトを示すことが示された。