Multi‐marker algorithms based on CXCL13, IL‐10, sIL‐2 receptor, and β2‐microglobulin in cerebrospinal fluid to diagnose CNS lymphoma

• Published in: Cancer medicine (Malden, MA) MA), 2020-06, Vol.9 (12), p.4114-4125
• Main Authors: Maeyama, Masahiro, Sasayama, Takashi, Tanaka, Kazuhiro, Nakamizo, Satoshi, Tanaka, Hirotomo, Nishihara, Masamitsu, Fujita, Yuichi, Sekiguchi, Kenji, Kohta, Masaaki, Mizukawa, Katsu, Hirose, Takanori, Itoh, Tomoo, Kohmura, Eiji
• Format: Article
• Language: English
• Subjects: Algorithms; beta 2-Microglobulin - cerebrospinal fluid; biomarker; Biomarkers; Biomarkers, Tumor - cerebrospinal fluid; Biopsy; Brain cancer; Brain diseases; Case-Control Studies; Central nervous system; central nervous system lymphoma; Central Nervous System Neoplasms - cerebrospinal fluid; Central Nervous System Neoplasms - diagnosis; Cerebrospinal fluid; Chemokine CXCL13 - cerebrospinal fluid; Chemokines; Chemotherapy; Clinical Cancer Research; Convulsions; CXCL13; CXCL13 protein; Cytokines; Follow-Up Studies; Humans; IL‐10; Interleukin-10 - cerebrospinal fluid; Ligands; Lymphocytes; Lymphoma; Lymphoma, Non-Hodgkin - cerebrospinal fluid; Lymphoma, Non-Hodgkin - diagnosis; Magnetic resonance imaging; Medical prognosis; Metastasis; Nervous system; Neurosurgery; Original Research; Patients; Prognosis; Prospective Studies; Radiation therapy; Receptors, Interleukin-2 - analysis; Retrospective Studies; Survival analysis; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3048

Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) β2‐microglobulin (β2‐MG), soluble IL‐2 receptor (sIL‐2R), and interleukin‐10 (IL‐10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C‐X‐C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case‐control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi‐marker diagnostic model using CSF CXCL13, IL‐10, β2‐MG, and sIL‐2R from the results of the case‐control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi‐marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi‐marker algorithms are important diagnostic tools for patients with CNS lymphoma. A comparison of the cerebrospinal fluid (CSF) concentrations of CXCL13 between CNS lymphomas and other CNS diseases. The CSF CXCL13 levels of CNS lymphoma were significantly higher than those of the other diseases. The CXCL13 expression levels increased in the CNS lymphoma specimens compared with the other tumor specimens. The multi‐marker prediction algorithms based on CSF CXCL13, IL‐10, sIL‐2R, and β2‐MG had excellent diagnostic performance.