AUTHOR=Holst Camilla Bjørnbak , Christensen Ib Jarle , Skjøth-Rasmussen Jane , Hamerlik Petra , Poulsen Hans Skovgaard , Johansen Julia Sidenius 

TITLE=Systemic Immune Modulation in Gliomas: Prognostic Value of Plasma IL-6, YKL-40, and Genetic Variation in YKL-40

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00478

DOI=10.3389/fonc.2020.00478

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Complex local and systemic immune dysfunction in glioblastoma (GBM) may affect survival. Interleukin (IL)-6 and YKL-40 are pleiotropic biomarkers present in the tumor microenvironment and involved in immune regulation. We therefore analyzed plasma IL-6, YKL-40, and genetic variation in YKL-40 and explored their ability to distinguish between glioma subtypes and predict survival in GBM.</p><p><bold>Methods:</bold> One hundred fifty-eight patients with glioma WHO grade II-IV were included in the study. Plasma collected at surgery was analyzed for IL-6 and YKL-40 (CHI3L1) by ELISA. CHI3L1 rs4950928 genotyping was analyzed on whole-blood DNA.</p><p><bold>Results:</bold> Neither plasma IL-6 nor YKL-40 corrected for age or rs4950928 genotype could differentiate GBM from lower grade gliomas. GC and GG rs4950928 genotype were associated with lower plasma YKL-40 levels (CC vs. GC, <italic>p</italic> = 0.0019; CC vs. GG, <italic>p</italic> = 0.01). Only 10 and 14 out of 94 patients with newly diagnosed GBM had elevated IL-6 or YKL-40, respectively. Most patients received corticosteroid treatment at time of blood-sampling. Higher pretreatment plasma IL-6 was associated with short overall survival (OS) [HR = 1.19 (per 2-fold change), <italic>p</italic> = 0.042] in univariate analysis. The effect disappeared in multivariate analysis. rs4950928 genotype did not associate with OS [HR = 1.30, <italic>p</italic> = 0.30]. In recurrent GBM, higher YKL-40 [HR = 2.12 (per 2-fold change), <italic>p</italic> = 0.0005] but not IL-6 [HR = 0.99 (per 2-fold change), <italic>p</italic> = 0.92] were associated with short OS in univariate analysis.</p><p><bold>Conclusion:</bold> In recurrent GBM high plasma YKL-40 may hold promise as a prognostic marker. In newly diagnosed GBM perioperative plasma IL-6, YKL-40, and genetic variation in YKL-40 did not associate with survival. Corticosteroid use may complicate interpretation of results.</p>