FGF2 as a potential prognostic biomarker for proneural glioma patients

Sooman, Linda; Freyhult, Eva; Jaiswal, Archita; Navani, Sanjay; Edqvist, Per‐Henrik; Pontén, Fredrik; Tchougounova, Elena; Smits, Anja; Elsir, Tamador; Gullbo, Joachim; Lennartsson, Johan; Bergqvist, Michael; Ekman, Simon

doi:10.3109/0284186x.2014.951492

Cited by 27 publications

(24 citation statements)

References 38 publications

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“…A TMA was constructed from a retrospective cohort of adult patients with high-grade gliomas receiving RT at our hospital, as previously described [15]. Tumors diagnosed as astrocytomas WHO grade III and IV, based on histological classification were collected for the present study.…”

Section: Resultsmentioning

confidence: 99%

“…For PROX1 protein screening we selected 86 astrocytomas WHO grade III and IV from a TMA of a previously described retrospective cohort of 96 adult patients with high-grade gliomas [15]. Oligodendroglial tumors were excluded based on histological tumor diagnosis.…”

Section: Methodsmentioning

confidence: 99%

“…All patients received RT, concomitant and adjuvant TMZ was not used consistent with standard protocols at that time. Thirty-one patients received chemotherapy and 19 patients had proton radiation as second-line treatment [15]. Survival was defined as the time point between surgery and date of death.…”

Section: Methodsmentioning

confidence: 99%

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PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

et al. 2016

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PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

et al. 2016

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“…Previous studies indicated the potential prognostic value and clinicopathological signi cance of CD44 expression in glioma patients. However, the eligible studies included in this meta-analysis were diversi ed and the results were contradictory [52,53,[55][56][57][58][59][60][61][62][63][64][65][66]. The present meta-analysis systematically analyzed the prognostic impact of CD44s expression on glioma patients.…”

Section: Discussionmentioning

confidence: 99%

“…Fourteen studies [52,53,[55][56][57][58][59][60][61][62][63][64][65][66], including 743 patients, reported overall survival (OS) data using univariate analysis (Table 1). With substantial heterogeneity (P<0.0001, I 2 =72.2%), a pooled analysis in a random-effects model showed increased CD44s expression in glioma patients predicted reduced OS (pooled HR =1.63, 95% CI= [1.16, 2.29], P=0.005) ( Fig.…”

Section: Correlation Between Cd44s Expression and Overall Survivalmentioning

confidence: 99%

Clinicopathological and Prognostic Significance of CD44s and CD44v6 Expression in Patients with Glioma: A Systematic Review and Meta-analysis

Xie¹,

Zhang²,

Xing³

et al. 2020

Preprint

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Background: Cancer stem cell surface marker CD44 has been revealed to promote tumor growth, progression, and metastasis in gliomas. Although the prognostic and clinicopathological value of CD44 standard form (CD44s) and its variant isoform CD44v6 expression in glioma patients has been evaluated in several independent studies, their results remained controversial. Therefore, we performed this meta-analysis to investigate the prognostic and clinicopathological association of CD44s/CD44v6 expression with glioma patients.Methods: A comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.Results: A total of 43 studies with 2817 glioma patients were included in this meta-analysis. Pooled results indicated that positive expression of CD44s was significantly associated with poorer overall survival (OS, univariate analysis, HR =1.63, 95% CI= [1.16–2.29], P=0.005; multivariate analysis, HR=2.14, 95%CI= [1.21, 3.78], P=0.009), and reduced progression-free survival (PFS) in the univariate analysis (HR=2.09, 95% CI= [1.59, 2.75], P<0.00001), but not with PFS in the multivariate analysis (P>0.05) or tumor recurrence (P>0.05). CD44 expression was significantly upregulated in glioma tissues when compared with non-tumorous brain tissues (CD44s, OR=31.31, 95% CI= [15.22, 64.43], P<0.00001; CD44v6, OR=13.18, 95% CI= [5.51, 31.51], P<0.00001). In particular, CD44 expression was preferentially expressed in high-grade gliomas (grade III-IV vs. grade I-II, CD44s, OR=4.67, 95% CI= [3.18, 6.87], P<0.00001; CD44v6, OR=2.06, 95% CI= [1.21, 3.51], P=0.008). CD44s expression was lower in brain metastases than that in primary gliomas (OR=0.25, 95% CI= [0.10, 0.60], P=0.002), however, higher expression of CD44v6 was detected in brain metastases when compared with primary gliomas (OR=49.44, 95% CI= [13.06, 187.22], P<0.00001).Conclusions:This meta-analysis revealed the prognostic value of CD44s expression and clinicopathological significance of CD44s/CD44v6 expression in gliomas. Increased CD44s expression can predict worse prognosis of glioma patients. Particularly, CD44s is an independent prognostic factor for poor OS of glioma patients. Both CD44s and CD44v6 were glioma patients predominantly expressed in glioma tissues, especially in high-grade gliomas. Additionally, CD44v6 is a potential diagnostic biomarker for differentiating brain metastases from primary gliomas in individual cases. Therapeutic strategies targeting CD44 in gliomas should be further explored in the future.

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