BICD Cargo Adaptor 1 (BICD1) Downregulation Correlates with a Decreased Level of PD-L1 and Predicts a Favorable Prognosis in Patients with IDH1-Mutant Lower-Grade Gliomas

SIMPLE SUMMARY: The hypoxic inducible factor 1A (HIF1A) pathway has been known to play an important role in tumor progression in various cancers, including lower-grade (Grade II/III) gliomas (LGGs). An in silico analysis using 34 genes associated with the activity of the HIF1A pathway demonstrated that the BICD cargo adaptor 1 (BICD1) gene is a potential prognostic marker in LGGs. Moreover, BICD1 gene (BICD1) expression was positively correlated with CD274, GSK3B, HGF, and STAT3 expression in LGGs. Importantly, BICD1 downregulation was significantly associated with well-known favorable prognostic markers, such as a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR and younger patient age, in LGGs. Therefore, our findings present BICD1 as a new prognostic biomarker to more precisely predict the clinical outcomes of LGG patients in coordination with those well-known biomarkers. ABSTRACT: Although several biomarkers have been identified to predict the prognosis of lower-grade (Grade II/III) gliomas (LGGs), we still need to identify new markers to facilitate those well-known markers to obtain more accurate prognosis prediction in LGGs. Bioinformatics data from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Cancer Cell Line Encyclopedia (CCLE) datasets were used as the research materials. In total, 34 genes associated with the HIF1A pathway were analyzed using the hierarchical method to search for the most compatible gene. The BICD cargo adaptor 1 (BICD1) gene (BICD1) was shown to be significantly correlated with The hypoxic inducible factor 1A (HIF1A) expression, the World Health Organization (WHO) grade, and IDH1 mutation status. In addition, BICD1 downregulation was significantly correlated with a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR, and younger patient age in the enrolled LGG cohort. Moreover, BICD1 expression was significantly upregulated in wild-type IDH1 LGGs with EGFR mutations. Kaplan–Meier survival analysis revealed that BICD1 downregulation predicts a favorable overall survival (OS) in LGG patients, especially in those with IDH1 mutations. Intriguingly, we found a significant correlation between BICD1 downregulation and a decreased level of CD274, GSK3B, HGF, or STAT3 in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.