Increased LGALS3 expression independently predicts shorter overall survival in patients with the proneural subtype of glioblastoma

Abstract

In the current study, we tried to study the expression of LGALS3 and LGALS3BP, their potential as prognostic markers and the possible genetic/epigenetic mechanisms underlying their dysregulation in different subtypes of glioblastoma (GBM). An in silico retrospective study was performed using large online databases. Results showed that LGALS3 and LGALS3BP were upregulated at both RNA and protein levels in GBM tissue and were generally associated with shorter overall survival (OS) in GBM patients. However, in subgroup analysis, we only found the association in proneural subtype. The copy number alterations did not necessarily lead to LGALS3/LGALS3BP dysregulation. In the proneural subtype of GBM patients, hypermethylation of the two CpG sites (cg19099850 and cg17403875) was associated with significantly lower expression of LGALS3. In univariate and multivariate analysis, LGALS3 expression independently predicted shorter OS in the proneural subtype of GBM (HR: 1.487, 95% CI: 1.229-1.798, P < 0.001), after adjustment of age, gender, IDH1 mutations, temozolomide chemotherapy, radiotherapy and LGALS3BP expression. In comparison, LGALS3BP lost the prognostic value in multivariate analysis. Based on these findings, we infer that LGALS3 expression serves as an independent biomarker of shorter OS in the proneural subtype of GBM, the expression of which might be regulated in an epigenetic manner.