Role of miRNA‑21 in the diagnosis and prediction of treatment efficacy of primary central nervous system lymphoma

Luo

et al. 2019

OTT

ObjectivePrimary testicular diffuse large B-cell lymphoma (PT-DLBCL) is relatively rare, and risk factors of this disease are still not well understood. This study aims to identify clinical features and prognostic factors of PT-DLBCL patients.MethodsThirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed.ResultsThe median age of the patients was 57 (range 36–76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4–6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan–Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028).ConclusionOur work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS.

Section: Introductionmentioning

confidence: 99%

<p>Prognostic Significance of LDH Ratio in Serum/Cerebral Spinal Fluid of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma</p>

Luo

et al. 2019

OTT

“…MiRNA expression of PCNSL has been studied using different methods such as RT-PCR [28-38], microarray [36, 39], in situ hybridization [37, 38], next-generation sequencing (NGS) [35] and NanoString [38] technologies on various tissue types including brain biopsy specimens (FFPE [32, 37, 39] or fresh [36]), cerebrospinal fluid (CSF) [28-31, 33, 38] and peripheral blood [35], serum [34] or plasma [33]. It has been shown and further confirmed that the combined detection of miR-21, miR-19b and miR-92a in CSF allowed a reliable diagnosis of PCNSL.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, these miRNAs emerge as promising tools in treatment monitoring and follow-up [28, 29], similarly to U2 small nuclear RNA fragments [30]. In addition, plasma miR-21 may serve as a diagnostic [33], and serum miR-21 both as a diagnostic and prognostic marker for PCNSL [34]. Other miRNAs with prognostic value in PCNSL include miR-151a-5p and miR-151b, together with 10 additional miRs [35].…”

Section: Introductionmentioning

confidence: 99%

“…Other miRNAs with prognostic value in PCNSL include miR-151a-5p and miR-151b, together with 10 additional miRs [35]. CSF levels of miRlzl21 may have potential as a predictor of chemotherapeutic effect [33]. Measuring miR-30c in the CSF can differentiate between PCNSL and SCNSL, as elevated levels of miR-30c have pathobiological significance in SCNSL [31].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct microRNA expression signatures of primary and secondary central nervous system lymphomas

Sebestyén¹,

Nagy²,

Marosvári³

et al. 2021

Preprint

Central nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma, PCNSL) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma, SCNSL). Dysregulated expression of microRNAs (miRNAs) is associated with various pathological processes and miRNA expression patterns may have diagnostic, prognostic and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. Here, we performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by a detailed statistical analysis to identify potential novel biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns and survival. We describe the general expression patterns of miRNAs across CNS lymphoma samples and identified 31 differentially expressed miRNAs between primary and secondary groups. Additionally, we identified 7 more miRNAs associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, we defined a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared to the rest of the cases. Finally, we identified differentially regulated pathways in the above comparisons and assessed the utility of miRNA expression patterns in predicting survival. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in their pathogenesis, and provides the basis for future research.

“…Recently, discovery of molecular biomarkers from the cerebrospinal fluid (CSF) 4 and the serum 5 have become an area of extensive research. Among the novel biomarkers, microRNAs (miRNAs) have been considered in PCNSL diagnosis because the primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) has a distinct miRNA signature compared to that in the germinal center (GC)-DLBCL and the non-GC-DLBCL 6 . Despite this finding, there is a limited clinical application of miRNA.…”

Section: Introductionmentioning

confidence: 99%

miR-432 is a novel biomarker for PCNSL and is associated with cell adhesion: An integrated bioinformatics analysis

Ma¹

2020

Preprint

Background: Primary central nervous system lymphoma (PCNSL), a rare form of the non-Hodgkin's lymphoma (NHL), usually has a poor prognosis, and molecular pathogenesis of PCNSL has not been fully elucidated. Here, potential miRNA biomarkers were investigated in patients with PCNSL using an integrated bioinformatics analysis. Methods: Expression profile arrays (GSE122011, GSE139031, and GSE25297) were obtained from the Gene Expression Omnibus (GEO). Free-scale miRNA co-expression networks were constructed with 27 PCNSL patients from GSE122011 by the weighted gene co-expression network analysis (WGCNA) in order to identify candidate biomarkers. Subsequently, miRNA-miRNA networks were visualized with the Cytoscape. Expression of candidate miRNAs was assessed in serum samples from GSE139031, including 42 PCNSL patients and 77 non-cancer individuals, and the sensitivity and the specificity were assessed by the receiver operating characteristic (ROC) curve. From GSE25297, differentially expressed genes (DEGs) from the PCNSL tissues (n = 7) and the normal lymph nodes (n = 7) were compared, target genes of candidate miRNAs were downloaded from TargetScan database, and target genes that were also down-regulated in GSE25297 were used to construct the protein-protein interaction (PPI) networks and for the gene ontology (GO) analysis. Results: miRNAs were clustered into two groups with 8 modules in 27 patients with PCNSL. One group consisted of the yellow and the turquoise modules, and the second group consisted of the other six modules. In the miRNA-miRNA network, the highest nodes were observed between miR-432 and miR-330-3p, which were from the yellow and the turquoise modules, and only miR-432 was closely associated with both the yellow (0.977, P = 2.88E -18 ) and the turquoise modules (0.525, P = 0.005). Additionally, patients with PCNSL had higher serum miR-432 expression compared with that in the non-cancer controls in GSE139031, and miR-432 has a higher accuracy for discriminating between PCNSL and non-cancer samples (AUC: 0.77; 95% CI: 0.6923 to 0.8550). For target genes of miR-432, RASGRF , DGKG , SMIM22 , SPOCD1 , NRCAM , CNTN2 , PTPRD , POTED , IGSF3 , SLC24A2 , CTNND2 , AIF1L , TMEM229A , GLDN , and MOBP were down-regulated in the PCNSL tissues. Among them, CTNND2 , GLDN , NRCAM , and PTPRD were associated with cell adhesion. Conclusion: Up-regulated miR-432 expression is a novel biomarker for patients with PCNSL and may be associated with cell adhesion.