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Chitinase 3-Like 2: A Novel Biomarker Expressed in Peritumoral Brain Zone of Glioblastoma Is Associated With Tumor Recurrence and Poor Patient Prognosis

Groups and Associations Nimbalkar VP, Kruthika BS, Sravya P, Rao S, Sugur HS, Chickabasaviah YT, Somanna S, Arivazhagan A, Kondaiah P, Santosh V.
American Journal of Clinical Pathology 2022

Objectives: We aimed to evaluate the expression pattern of chitinase 3-like 2 (CHI3L2) in the tumor core and peritumoral brain zone (PBZ) of newly diagnosed glioblastoma (GBM) in recurrent tumors and its association with patient prognosis.

Methods: The study was conducted on three sample sets derived from different patient cohorts. Messenger RNA (mRNA) expression of CHI3L2 in the tumor core and PBZ (n = 34) compared with control (n = 20) tissues was studied by quantitative polymerase chain reaction in sample set 1. Sample set 2 included 19 paired, primary-recurrent GBM tissues. Sample set 3 comprised 82 GBM tissues of patients with treatment and follow-up information. Immunohistochemistry (IHC) was performed on all three sample sets.

Results: mRNA expression of CHI3L2 was significantly higher in the tumor core and PBZ compared with control (P < .0001). By IHC, CHI3L2 showed strong cytoplasmic staining in tumor cells. Recurrent tumors had a higher expression of CHI3L2 compared with primary tumors (P = .007). Survival analysis showed CHI3L2 expression was associated with shorter overall survival (P = .034) and progression-free survival (P = .010), which was in line with The Cancer Genome Atlas cohort (P = .043).

Conclusions: High expression of CHI3L2 in the tumor core and PBZ, as well as its association with tumor recurrence and poor patient prognosis, suggests it might be contributing to tumor spread and recurrence.

Keywords: CHI3L2; Glioblastoma; PBZ; Prognosis; Tumor recurrence.