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The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis.

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机构： [1]Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, Beijing 100070, China. [2]Department of Hematology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China [3]Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [4]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. [5]Department of Hematology, Chinese PLA General Hospital, Beijing, China. [6]Neuroimaging Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [7]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

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Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis.In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed.The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P < 0.05). The relative mRNA expression level of MTOR in PCNSL samples was significantly increased (P = 0.013). Correlation analysis revealed that the expression of p-mTOR was correlated with that of p-AKT, p-S6, p-4E-BP1. PTEN deletion was found in 18.9% of PCNSL samples and was correlated with the expression of p-AKT (P = 0.031). Correlation analysis revealed that the PCNSL relapse rate in the p-mTOR-positive group was 64.5%, significantly higher than that in the negative group (P = 0.001). Kaplan-Meier survival analysis showed inferior progression-free survival (PFS) in the p-mTOR- and p-S6-positive groups (P = 0.002 and 0.009, respectively), and PTEN deletion tended to be related to shorter overall survival (OS) (P = 0.072). Cox regression analysis revealed p-mTOR expression as an independent prognostic factor for a shorter PFS (hazard ratio (HR) =7.849, P = 0.046).Our results suggest that the PI3K/AKT/mTOR signaling pathway is aberrantly activated in PCNSL and associated with a poor prognosis, which might indicate new therapeutic targets and prognostic factors.© 2022. The Author(s).

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出版当年[2021]版：

大类 | 2 区

医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 2 区

医学

小类 | 3 区肿瘤学

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出版当年[2020]版：

Q2 ONCOLOGY

最新[2023]版：

Q2 ONCOLOGY

影响因子： 3.4 最新[2023版] 3.8 最新五年平均 4.43 出版当年[2020版] 4.372 出版当年五年平均 3.15 出版前一年[2019版] 4.638 出版后一年[2021版]

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第一作者机构： [1]Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, Beijing 100070, China. [2]Department of Hematology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

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