New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL)

Abstract

Background 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. Methods This study is a retrospective cohort study; 35 immunocompetent PCNSL‐DLBCL patients had their gene expression (RT‐qPCR) normalized to internal control gene GUSB. Results 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. Conclusions Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.

Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection

“…Our study revealed that 86.5% of the patients had high Ki-67 expression (Ki-67 index > 50%), which is consistent with the literature and indicates rapid growth of tumor cells [12]. Reis et al [13] reported that increased expression of Bcl-6 in patients with PCNSL was associated with an extended period of survival, indicating its predictive value. Therefore, the lower expression of Bcl-6 in HIV-related PCNSL may indicate a poorer prognosis than in IC-PCNSL.…”

Extranodal lymphoma: pathogenesis, diagnosis and treatment

“…The apoptosis pathway dysregulation in extranodal lymphomas is often due to abnormalities in key regulators like BCL2, p53, and MYC [ 45 – 47 ]. For example, upregulation of P53 may inhibit apoptosis in NKTCL [ 45 , 46 ].…”

“…For example, upregulation of P53 may inhibit apoptosis in NKTCL [ 45 , 46 ]. Overexpression of MYC and BCL2 is frequently seen in patients with B-cell extranodal lymphomas [ 47 , 48 ] and PTCL [ 49 , 50 ]. BCL2 inhibitors like venetoclax [ 49 ] and obatoclax [ 50 ] can restore apoptosis.…”

“…MYC (also called c-MYC in protein level) is one of the most prominent prognostic factors in PCNSL and can function at three levels: RNA, DNA, and protein. In a retrospective analysis, Gomes Candido Reis D et al identified overexpression of MYC as a poor prognostic indicator of PCNSL [ 47 ]. RNA was isolated from 35 formalin-fixed and paraffin-embedded (FFPE) tissue samples.…”