CHI3L1 as a Prognostic Biomarker and Therapeutic Target in Glioma

Abstract

The role of Chitinase-3-like protein 1 (CHI3L1) in tumor progression has been gradually clarified in different kinds of solid tumors. Hence, we aim to elucidate its prognostic value for glioma. In this study, we analyzed RNA sequencing data combined with corresponding clinical information obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed genes (DEGs) were acquired based on CHI3L1 expression profiles and were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Cox regression, least absolute shrinkage and selection operator (LASSO) regression methods, along with a nomogram, were employed to establish a predictive model. Compared with the corresponding non-tumor tissues, CHI3L1 expression was significantly upregulated in various types of solid tumors, correlating with poor clinical outcomes including glioma. GO analysis identified oxidative stress-related genes (ORGs) that were differentially expressed and modulated by CHI3L1, with 11 genes subsequently identified as potential predictors, using Univariate-Cox regression and LASSO regression. In addition, an index of oxidative stress-related genes (ORGI) was established, demonstrating its prognostic value in conjunction with CHI3L1 expression. The aberrant expression of CHI3L1 was proved in glioma patients through immunohistochemistry (IHC). Meanwhile, the knockdown of CHI3L1 inhibited glioma growth in vitro, and real-time Quantitative PCR (qPCR) confirmed decreased ORG expression upon CHI3L1 knockdown, suggesting the potential prognostic value of CHI3L1 as a therapeutic target for glioma.