Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma

Abstract

Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P < .05, MS (163 ng/mL); P < .01, GBM (41 ng/mL); P < .01, or healthy controls (319 ng/mL); P < .01. The area under the ROC curve was 0.865 [95 % confidence interval (CI) 0.745-0.985] for differentiating CNSL and patients with inflammatory CNS disease; 0.956 (95 % CI 0.898-1.000) for CNSL and MS patients; 0.988 (95 % CI 0.964-1.000) for CNSL and GBM patients, and 0.915 (95 % CI 0.834-0.996) for CNSL patients and healthy controls. In multivariate analysis, high CSF OPN level was associated with shorter progression-free (HR 1.61, 95 % CI 1.13-2.31; P = .009) and overall survival (HR 1.52, 95 % CI 1.04-2.21; P = .029). CSF OPN is a potential biomarker in CNSL.

Osteopontin at the Crossroads of Inflammation and Tumor Progression

“…OPN gene is upregulated in primary central nervous system lymphomas (PCNSL) as compared to that in diffuse large B cell lymphoma (DLBCL) [208], and its levels in cerebrospinal fluid (CSF) appear to be an independent predictor of shorter progression-free and overall survival [209]. Serum levels of OPN also predict response to therapy and survival in DLBCL [210, 211] and serum and CSF levels were correlated to tumor bulk and response to therapy in children with acute lymphoblastic leukemia (ALL) [211].…”

Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review

“…The diagnostic values of markers, as derived from the included studies, are listed for PCNSL (Table ) (Kersten et al , ; Murase et al , ; Roy et al , ; Baraniskin et al , , , ; Sasayama et al , ; Rubenstein et al , ; Mao et al , ; Kuusisto et al , ; Sasagawa et al , ; Viaccoz et al , ; Mabray et al , ; Nguyen‐Them et al , ; Song et al , ; Strehlow et al , ; Ikeguchi et al , ; Thaler et al , ) and for SCNSL (Table ) (Ernerudh et al , ; Kersten et al , ; Kara et al , ; Muñiz et al , ). Some of the included articles reported the diagnostic values for PCNSL and SCNSL as one patient group (Roy et al , ), these results are also included in Table .…”

“…Another pro‐inflammatory cytokine, osteopontin, is associated with progression, metastatic spread and poor prognosis in many malignancies (Strehlow et al , ). In a combined patient group of PCNSL and SCNSL, CSF osteopontin showed a sensitivity of 87% and a specificity of 86%, compared to control patients, with a cut‐off value of 400 ng/ml (Strehlow et al , ). Serum osteopontin demonstrated poor diagnostic value in this population.…”

“…Hence, risk of bias concerning the index test was high in the other thirteen studies. There was no reference standard described in six studies (Murase et al , ; Kara et al , ; Roy et al , ; Rubenstein et al , ; Mao et al , ; Strehlow et al , ) and there was possible risk of bias in the way the used reference standard classified the presence or absence of CNS lymphoma in three studies (Ernerudh et al , ; Mavligit et al , ; Muñiz et al , ).…”

Optimization of CSF biological investigations for CNS lymphoma diagnosis

“…Other non‐cell‐based approaches such as neopterin or osteopontin quantification in the CSF, as well as detection of cfDNA, have been the subject of several publications recently, but further studies are still needed . Of note, we evaluated IGH PCR on cfDNA obtained from CSF supernatants on a limited number of samples of the training cohort, which yielded several interesting preliminary results.…”