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Expression and biological processes of CHI3L2 in brain glioma and its impact on patient prognosis
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Abstract:
Objective: To investigate the expression and biological processes of chitinase-3-like protein 2 (CHI3L2) in brain gliomas and its impact on clinical prognosis of patients based on bioinformatics methods. Methods: With Chinese Glioma Genome Atlas (CGGA) serving as the training set (n = 325) and The Cancer Genome Atlas (TCGA) as the validation set (n = 702), the relationship between CHI3L2 and clinicopathologic features of brain glioma patients, as well as its prognostic value and biological processes were analyzed and cross-validated. Kaplan-Meier method was used for survival analysis. Cox regression model was employed to analyze the association between CHI3L2 expression and relevant clinicopathological features as well as prognosis of brain glioma patients. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of CHI3L2 for brain glioma. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Sene Set Variation Analysis (GSEA) were conducted to assess the potential biological processes associated with CHI3L2 in brain glioma. A Nomogram incorporating CHI3L2 and other relevant factors was constructed, and calibration curve and C-Index value were used to evaluate the Nomogram’s accuracy in prognosis prediction. The protein and mRNA expression levels of CHI3L2 in normal astrocyte HA1800, as well as glioma U215 and U87 cells, were assessed using Western blotting and qPCR, respectively. Immunohistochemistry was performed on 7 normal brain samples, 5 lowgrade glioma samples (LGG, WHO Ⅰ - Ⅱ), and 6 glioblastoma sample (GBM, WHO Ⅳ) that collected from the Department of Pathology at Changsha Central Hospital, with an aim to verify the expression of CHI3L2 in normal brain tissues and glioma tissues of different grades. Results: CHI3L2 was highly expressed in patients with GBM (P < 0.000 1), non-1p/19q coding glioma (P < 0.000 1), IDH-wild type glioma (P < 0.000 1), and non-MGMT methylation glioma (P < 0.01), showing certain predictive value for GBM. Additionally, CHI3L2 was identified as an independent prognostic factor for overall survival (OS) in glioma patients (P < 0.001). The constructed nomogram exhibited good predictive accuracy for patient prognosis. Furthermore, CHI3L2 was significantly associated with immune cell infiltration level, tumor immune microenvironment, and immune cells in LGG and GBM. Elevated CHI3L2 protein (P < 0.05) and mRNA (P < 0.000 1) levels in gliomas were correlated with higher malignant grade, as further confirmed by immunohistochemistry results. Conclusion: CHI3L2 expression is intricately associated with the malignancy, clinicopathological characteristics, and prognosis of brain glioma. It actively participates in the tumor microenvironment and immune infiltration within glioma, thereby representing a promising therapeutic target for glioma treatment.
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