Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and carcinoma with CNS metastasis

J Neurooncol. 2018 May;137(3):455-462. doi: 10.1007/s11060-017-2742-z. Epub 2018 Jan 16.

Abstract

Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma [12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer neurological diseases, and compared PRGN levels among these disease groups. Median CSF PGRN levels in the CNS+ lymphoma group were significantly higher than in the CNS- lymphoma and control non-cancer groups; and were also significantly higher in the CNS+ carcinoma group than in the CNS- carcinoma and control groups, except for patients with infectious neurological disorders. Receiver operating characteristic curve analyses revealed that CSF PGRN levels distinguished CNS+ lymphoma from CNS- lymphoma and non-cancer neurological diseases [area under curve (AUC): 0.969]; and distinguished CNS+ carcinomas from CNS- carcinomas and non-cancer neurological diseases (AUC: 0.918). We report here, for the first time, that CSF PGRN levels are higher in patients with CNS+ lymphoma and carcinomas compared to corresponding CNS- diseases. This would imply that measuring CSF PGRN levels could be used to monitor CNS+ lymphoma and metastasis.

Keywords: Carcinoma; Central nervous system; Cerebrospinal fluid; Lymphoma; Metastasis; Progranulin.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / cerebrospinal fluid
  • Carcinoma / cerebrospinal fluid*
  • Carcinoma / drug therapy
  • Carcinoma / pathology
  • Central Nervous System Neoplasms / cerebrospinal fluid*
  • Central Nervous System Neoplasms / diagnostic imaging
  • Central Nervous System Neoplasms / secondary*
  • Cohort Studies
  • Female
  • Humans
  • Lymphoma / cerebrospinal fluid*
  • Lymphoma / drug therapy
  • Lymphoma / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / diagnosis*
  • Neoplasm Metastasis / drug therapy
  • Progranulins / cerebrospinal fluid*
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • GRN protein, human
  • Progranulins