大学院生の高 正圭先生が、中枢神経原発悪性リンパ腫（primary central nervous system lymphoma; PCNSL）の患者さんの予後を決定する因子として、リン酸化TOPK (phosphorylated T-LAK cell originated protein kinase; p-TOPK)が、これまでに報告されてきたバイオマーカーよりも高い精度を有していることを世界で初めて証明した研究です。
TOPKは、精巣や胎児組織以外では正常組織に発現していないものの、数多くの悪性腫瘍に発現していることが判明しつつある酵素で、p-TOPKの高発現は無増悪生存期間(PFS; HR=5.5, P=0.029)、生命予後(OS; HR=7.7, P=0.014)を有意に短縮することが判明しました。
A Voyage to Depth of Neuroscience Vol. 45
Koh M, Hayakawa Y, Akai T, Hayashi T, Tomita T, Nagai S, Kuroda S.
Neuropathology. 2018 Mar 25. doi: 10.1111/neup.12463. [Epub ahead of print]
This study aimed to assess whether T-lymphokine-activated killer cell-originated protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in patients with primary central nervous system lymphoma (PCNSL). This study enrolled 20 patients who were histologically diagnosed as having diffuse large B-cell type PCNSL between 2005 and 2015. Using surgical specimens, the expression of TOPK and phosphorylated TOPK (p-TOPK) was analyzed on immunohistochemistry. Clinical features such as age, sex, Karnofsky performance status (KPS), ocular involvement, deep brain structure involvement, the number of lesions, chemotherapy and radiation therapy were also collected. Impacts of TOPK/p-TOPK expression on their progression-free survival (PFS) and overall survival (OS) were examined with multivariate analysis. Median PFS/OS were 24.2 and 39.0 months, respectively. On immunostaining, the mean percentage of TOPK-positive cells was 35.5 ± 20.8%, and the mean number of p-TOPK-positive cells was 13.7 ± 15.7 cells/mm2 . The higher expression of p-TOPK was significantly related to multiple lesions (P = 0.003). Multivariate analysis demonstrated that only the higher expression of p-TOPK was an independent predictor to shorten both PFS (P = 0.029; hazard ratio (HR), 5.5; 95% confidential interval (CI), 1.2-25.3) and OS (P = 0.014; HR, 7.7; 95% CI, 1.5-41.3). These findings strongly suggest that p-TOPK may be a potent biomarker to determine the outcome of patients with PCNSL and to develop novel drugs to treat PCNSL.