Analysis of changes in expression of stem cell markers related to recurrent patterns of glioblastoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yamagata University
• Principal Investigator: Sonoda Yukihiko 山形大学, 大学院医学系研究科, 教授 (90302140)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Glioblastoma / TERT / FLAIR

Outline of Final Research Achievements

Glioblastoma has the poorest prognosis of adult brain tumors. The reasons for the poor prognosis of glioblastoma include the resistance to radiation chemotherapy. The presence of tumor stem cells is known to be a cause of resistance to chemoradiotherapy. In this study, we first examined whether the expression of tumor stem cell marker, CD133 was higher in recurrent tumors than in primary tumors. However, the expression of CD133 was not necessarily increased in recurrent tumors. So, we focused on the promoter mutation of the TERT gene, which is related to tumor invasiveness and recurrence. The ADC value of the FLAIR area around the contrast-ehnaced lesion was low in TERT mutation-positive cases, suggesting higher infiltration into the tumor periphery. In addition, the density of tumor cells was higher in TERT mutation cases. These results suggest that the degree of tumor cell invasion in glioblastoma varies depending on the presence or absence of TERT mutation.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は通常MRIの造影領域を摘出するのが標準的な手術法となっているが、再発は通常周囲のFLAIR高信号領域から生ずることが多い。したがってFLAIR高信号領域の摘出が近年注目を浴びている。FLAIR高信号領域は造影領域の数倍存在しており、その領域を摘出は通常困難である。今回の解析においてFLAIR高信号領域は腫瘍細胞の浸潤を示す、ADC値がFLAIR内でもバラつきがあり、特にTERTプロモータ変異のある症例では広範囲かつ高密度に腫瘍細胞が存在し、野生型ではその領域が限局していることが明らかとなった。本解析は今後の手術計画をするうえで有用な情報になり得る可能性がある。