MPTH-26. CXCL13 AND IL-10 IN CEREBROSPINAL FLUID (CSF) AS AN IMPORTANT BIOMARKER FOR PRIMARY CENTRAL NERVOUS SYSTEM CELL LYMPHOMA (PCNSL)

Abstract

Malignant lymphoma cells are known to secrete various cytokines and chemokines. We previously reported that the cerebrospinal fluid (CSF) level of interleukin-10 (IL-10) was useful biomarker for primary central nervous system lymphomas (PCNSLs). Recently, CXC chemokine ligand 13 (CXCL13) level in CSF was also reported to be useful biomarker for PCNSL. We analyzed CSF CXCL13 levels in the patients with various brain diseases, including PCNSLs, and compared with other biomarkers for PCNSLs. One hundred fourteen CSF samples were analyzed. Thirty samples were PCNSL (all diffuse larger B-cell lymphomas) and 84 samples were other brain diseases (brain tumors and inflammation diseases, etc). The CXCL13 levels were measured by ELISA. In addition, IL-10, IL-6, sIL-2 receptor, b2-microglobulin in CSF were measured and compared with CXCL13. Also, relationship between CXCL13 levels and prognosis (overall survival (OS) and progression-free survival (PFS)) was analyzed by Cox proportional hazards model. Mean CXCL13 concentrations in CSF were 1117.6 pg/ml (114.7~1934.7 pg/ml) and 29.1 pg/ml (0.3~345.1 pg/ml) in PCNSLs and other brain diseases, respectively. CXCL13 levels in CSF were significantly increased in PCNSLs compared with other brain diseases (p<0.0001). CSF CXCL13 levels had higher discrimination power of PCNSL (AUC=0.99) than CSF IL-10 (AUC=0.96), sIL-2 receptor (AUC=0.86), and b2-microglobulin (AUC=0.94). Also, diagnostic accuracy was improved by bivariate evaluation of CSF IL-10 and CXCL13. Furthermore, CXCL13 levels in CSF were statistically associated with OS (HR=1.001, 95% CI 1.000~1.002, p=0.03) and PFS (HR=1.001, 95% CI:1.000~1.002, p=0.02) in the patients with PCNSL. These results indicate that the CSF CXCL13 levels were quite useful diagnostic biomarker for the patients with PCNSLs. The measurement of both CXCL13 and IL-10 concentration in CSF could improve the diagnostic accuracy for PCNSLs. In addition, CSF CXCL13 may be a prognostic marker for PCNSL.