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Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis.

ABSTRACT: Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1(+) tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the "classical-like" (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients' outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1(+) cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1(-) cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1(+) cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma.

SUBMITTER: Xu SL

PROVIDER: S-EPMC4473324 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis.

Xu Sen-Lin SL Liu Sha S Cui Wei W Shi Yu Y Liu Qin Q Duan Jiang-Jie JJ Yu Shi-Cang SC Zhang Xia X Cui You-Hong YH Kung Hsiang-Fu HF Bian Xiu-Wu XW

American journal of cancer research 20150315 4

Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO gra ...[more]

PMID: 26101711

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Project description:BackgroundLactate dehydrogenase (LDH) is associated with the prognosis of many diseases, but the relationship between LDH and the poor prognosis (recurrence and death) of acute ischemic stroke (AIS) has not been fully clarified. This study aimed to investigate the association between admission LDH level and poor prognosis in patients with AIS.MethodsThis retrospective study enrolled AIS patients treated in Taizhou Hospital of Zhejiang Province from July 2019 to December 2019. Poor prognosis included AIS recurrence and all-cause death at 3, 6, and 18 months. The correction between LDH and poor prognosis or all-cause death was assessed. Lasso Cox expression and multivariate Cox expression analyses were used to evaluate the association of LDH with the risk of poor prognosis and all-cause death, respectively. A nomogram was constructed to evaluate the predictive Values of LDH for the poor prognosis and all-cause death of AIS.Results732 patients were included in the study. Multivariate analysis shows that admission LDH levels were significantly correlated with poor prognosis [odds ratio (OR),1.003; 95% confidence interval (95% CI), 1.001-1.005; P = 0.001] and all-cause death (OR, 1.005; 95% CI, 1.000-1.009; P = 0.031). The correlation analysis showed that admission LDH level was positively correlated with National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score. Time-dependent receiver operating characteristic (td-ROC) curves analysis showed that the AUC values of admission LDH level for predicting prognosis of AIS patients in 3-month, 6-month, 12-month and 18-month were 0.706 (95% CI, 0.604-0.810), 0.653 (95% CI, 0.583-0.723), 0.616 (95% CI, 0.556-60676) and 0.610 (95% CI, 0.552-0.680), respectively. And td-ROC also showed that the AUC values of admission LDH level for predicting all-cause death of AIS patients in 3-month, 6-month,12-month and 18-month were 0.861 (95% CI, 0.764-0.958), 0.824 (95% CI, 0.753-0.890), 0.726 (95% CI, 0.633-0.819) and 0.715 (95% CI, 0.622-0.807), respectively. The nomograms were constructed to create the predictive models of the poor prognosis and all-cause death of AIS.ConclusionHigher LDH levels are independently associated with poor prognosis and all-cause death of AIS.

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Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis.

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Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis.

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