Department of Hematology, Hemotherapy and Cell Therapy, Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.
Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.
Brain Behav. 2021 Apr;11(4):e02061. doi: 10.1002/brb3.2061. Epub 2021 Feb 16.
PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto-oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL.
This study is a retrospective cohort study; 35 immunocompetent PCNSL-DLBCL patients had their gene expression (RT-qPCR) normalized to internal control gene GUSB.
Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6-58.6), PFS was 41 months (95% CI: 19.7-62.4), and DFS was 59.2 months (95% CI 31.9-86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC ≥ 0.201 (HR 6.117; p = .003) was associated with worse 5-year OS. Relative gene expression of MYC ≥ 0.201 (HR 3.96; p = .016) and MGMT ≥ 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis.
Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.
PCNSL 是一种罕见的结外 NHL，预后较差。肿瘤发生与 BCR 下游和 NFkB 途径的过度激活有关。我们研究了 NFkB 途径（MYC、BCL2）、造血必需转录调节剂 LMO2、检查点调节途径 MGMT、转录因子 POU2F1、免疫检查点基因 PDCD1、原癌基因和转录抑制因子基因 BCL6 及其蛋白在 PCNSL 中的相对表达谱的预后。
本研究为回顾性队列研究；35 例免疫功能正常的 PCNSL-DLBCL 患者的基因表达（RT-qPCR）以内部对照基因 GUSB 进行归一化。
中位患者年龄为 62 岁，中位 OS 为 42.6 个月（95%CI：26.6-58.6），PFS 为 41 个月（95%CI：19.7-62.4），DFS 为 59.2 个月（95%CI 31.9-86.6）。发现 MYC（kappa=0.596，p=0.022）和 BCL2（kappa=0.426，p=0.042）的基因/蛋白表达之间存在中度相关性。MYC≥0.201（HR 6.117；p=0.003）的相对基因表达与较差的 5 年 OS 相关。MYC≥0.201（HR 3.96；p=0.016）和 MGMT≥0.335（HR 3.749；p=0.056）的相对基因表达与较差的 PFS 相关。年龄>60 岁和 IELSG 评分中/高也与预后不良相关。
MYC 过表达和 MGMT 过表达是 PCNSL 不良临床结局的预后标志物。
