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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.

SUBMITTER: He X

PROVIDER: S-EPMC6536958 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

He Xia X Zhang Sunfu S Chen Junchen J Li Dekang D

Cancer medicine 20190307 5

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. ...[more]

PMID: 30848102

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Project description:BackgroundSF3B1 mutations (SF3B1mut ) in myelodysplastic syndromes (MDS) frequently involve codon K700E and have a favorable prognosis. The prognostic effect of non-K700E SF3B1mut is uncertain.MethodsThe authors analyzed the clinicopathological features and outcomes of a single-institution series of 94 treatment-naive SF3B1mut MDS patients (18%) and 415 treatment-naive SF3B1wt MDS patients and explored the differences between K700E and non-K700E SF3B1mut MDS.ResultsFifty-five patients (59%) carried K700E. Recurrent non-K700E mutations (39 [41%]) included R625, H662, and K666. Compared with SF3B1mut K700E patients, non-K700E patients had a lower median absolute neutrophil count (1.8 vs 2.4; P = .005) and were frequently "high" according to the Revised International Prognostic Scoring System (19% vs 4%; P = .031). Non-K700E MDS was associated frequently with RUNX1 (26% vs 7%; P = .012) and exclusively with BCOR, IDH2, and SRSF2 mutations. A splicing analysis showed the differential distribution of alternatively spliced events and gene expression profiles between K700 and non-K700E MDS patients. The majority (at least 80%) of SF3B1mut K700E, SF3B1mut non-K700E, and SF3B1wt patients were treated with hypomethylating agents. Over a median follow-up of 16 months, SF3B1mut had superior overall survival (OS) in comparison with SF3B1wt in all MDS patients (not reached vs 25.2 months; P = .0003), in patients with low-grade MDS, and in patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS). Compared with SF3B1wt , SF3B1mut K700E had superior outcomes in all MDS (median OS, 25 months vs not reached; P = .0001), in low-grade MDS (median OS, 41.3 months vs not reached; P = .0015), and in MDS-RS (median OS, 22.3 months vs not reached; P = .0001), but no significant difference was seen between non-K700E and SF3B1wt MDS. By multivariable analysis, the absence of SF3B1mut K700E mutations was independently associated with the prognosis.ConclusionsThis study highlights the importance of the SF3B1 mutation subtype in MDS risk assessment.Lay summaryMyelodysplastic syndromes (MDS) with SF3B1 mutations are regarded as having a favorable prognosis by both the World Health Organization and the International Working Group for the Prognosis of Myelodysplastic Syndromes. However, this article shows that only MDS patients with SF3B1 K700E mutations have a favorable prognosis (and not MDS patients with SF3B1 mutations involving other codons). This has important implications for refining future MDS subclassification and risk assessment criteria.

Dataset Information

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

Publications

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

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