The predominant expression of cancer stem cell marker ALDH1A3 in tumor infiltrative area is associated with shorter overall survival of human glioblastoma.
Aged
Aldehyde Oxidoreductases
/ analysis
Biomarkers, Tumor
/ analysis
Brain
/ pathology
Brain Neoplasms
/ mortality
Case-Control Studies
DNA Methylation
DNA Modification Methylases
/ genetics
DNA Repair Enzymes
/ genetics
Female
Gene Expression Regulation, Neoplastic
Glioblastoma
/ mortality
Humans
Male
Middle Aged
Neoplastic Stem Cells
/ metabolism
Neurosurgical Procedures
Prognosis
Promoter Regions, Genetic
/ genetics
Tumor Suppressor Proteins
/ genetics
Up-Regulation
ALDH1A3
Cancer stem cell marker
Overall survival
Peritumoral edema
Primary glioblastoma
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
17 Jul 2020
17 Jul 2020
Historique:
received:
26
05
2020
accepted:
08
07
2020
entrez:
19
7
2020
pubmed:
19
7
2020
medline:
9
2
2021
Statut:
epublish
Résumé
ALDH1A3 is a cancer stem cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive role of ALDH1A3 in GBM remains unclear. This study attempted to investigate the expression of ALDH1A3 in human GBM tissues and its association with clinical parameters. Thirty primary GBM and 9 control were enrolled in this study. ALDH1A3 mRNA and protein expression levels were detected by RT ALDH1A3 protein level, but not mRNA level, in a subgroup of GBM was significantly higher than that in the control group. ALDH1A3 immunoreactivity was detected heterogeneously in individual GBMs. Fifteen of 30 cases showed a positive of ALDH1A3 immunoreactivity which was predominantly observed in the tumor infiltrative area (TI). Double immunofluorescence staining revealed a co-localization of ALDH1A3 with GFAP in glial-shaped cells and in tumor cells. ALDH1A3 immunoreactivity was often merged with CD44, but not with CD68. Moreover, ALDH1A3 expression was positively associated with the tumor edema grade and inversely with overall survival (OS) (median OS: 16 months vs 10 months), but with neither MGMT promoter methylation status nor Ki67 index in GBM. An upregulation of ALDH1A3 was accompanied by a reduced expression of STAT3β and p-STAT3β. Inter- and intra-tumoral heterogeneous expression of ALDH1A3 was exhibited in GBMs. A high immunoreactivity of ALDH1A3 in tumor infiltrative area was associated with shorter OS, especially in patients with MGMT promoter methylation. Our findings propose ALDH1A3 not only as a predictive biomarker but also as a potential target for personalized therapy of GBM.
Sections du résumé
BACKGROUND
BACKGROUND
ALDH1A3 is a cancer stem cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive role of ALDH1A3 in GBM remains unclear. This study attempted to investigate the expression of ALDH1A3 in human GBM tissues and its association with clinical parameters.
METHODS
METHODS
Thirty primary GBM and 9 control were enrolled in this study. ALDH1A3 mRNA and protein expression levels were detected by RT
RESULTS
RESULTS
ALDH1A3 protein level, but not mRNA level, in a subgroup of GBM was significantly higher than that in the control group. ALDH1A3 immunoreactivity was detected heterogeneously in individual GBMs. Fifteen of 30 cases showed a positive of ALDH1A3 immunoreactivity which was predominantly observed in the tumor infiltrative area (TI). Double immunofluorescence staining revealed a co-localization of ALDH1A3 with GFAP in glial-shaped cells and in tumor cells. ALDH1A3 immunoreactivity was often merged with CD44, but not with CD68. Moreover, ALDH1A3 expression was positively associated with the tumor edema grade and inversely with overall survival (OS) (median OS: 16 months vs 10 months), but with neither MGMT promoter methylation status nor Ki67 index in GBM. An upregulation of ALDH1A3 was accompanied by a reduced expression of STAT3β and p-STAT3β.
CONCLUSIONS
CONCLUSIONS
Inter- and intra-tumoral heterogeneous expression of ALDH1A3 was exhibited in GBMs. A high immunoreactivity of ALDH1A3 in tumor infiltrative area was associated with shorter OS, especially in patients with MGMT promoter methylation. Our findings propose ALDH1A3 not only as a predictive biomarker but also as a potential target for personalized therapy of GBM.
Identifiants
pubmed: 32680476
doi: 10.1186/s12885-020-07153-0
pii: 10.1186/s12885-020-07153-0
pmc: PMC7368792
doi:
Substances chimiques
Biomarkers, Tumor
0
Tumor Suppressor Proteins
0
Aldehyde Oxidoreductases
EC 1.2.-
aldehyde dehydrogenase (NAD(P)+)
EC 1.2.1.5
DNA Modification Methylases
EC 2.1.1.-
MGMT protein, human
EC 2.1.1.63
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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