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Rab27a was identified as a prognostic biomaker by mRNA profiling, correlated with malignant progression and subtype preference in gliomas.

Wang H, Zhao Y, Zhang C, Li M, Jiang C, Li Y - PLoS ONE (2014)

Bottom Line: Mutations in this gene are associated with Griscelli syndrome type 2.Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration.The 3 validation datasets revealed similar findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

ABSTRACT

Purpose: Rab27a belongs to the Rab small GTPase superfamily. The protein is membrane-bound and may be involved in protein transport and small GTPase-mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. However, the prognostic and molecular features of gliomas with Rab27a expression are still unclear.

Experimental design: We used a whole-genome mRNA expression microarray dataset of 220 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set. In this set, 220 gliomas, consisting of 97 WHO Grade II gliomas, 34 WHO Grade III gliomas, and 89 WHO Grade IV gliomas, were analyzed using the Kaplan-Meier method. To validate the protein expression of Rab27a, we assayed another 162 glioma samples by immunohistochemistry. Three additional datasets were obtained as validation sets. Gene ontology (GO) analysis and gene set variation analysis (GSVA) were used for the functional annotation of Rab27a in 89 WHO Grade IV gliomas.

Results: Rab27a was significantly associated with grade progression and high mortality in all grades of glioma in the discovery set. Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration. The 3 validation datasets revealed similar findings. Rab27a was more highly expressed in gliomas than in normal brain tissues, and its expression increased with glioma grade progression.

Conclusions: Rab27a expression was significantly associated with grade progression and worse prognosis in all grades of gliomas, suggesting Rab27a as a novel biomarker with potentially important therapeutic implications.

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Related in: MedlinePlus

Gene set variation analysis with Rab27a expression.Gene set variation analysis with Rab27a expression was analyzed using the GSVA package. Gene expression signatures of migration were generated from the GO list. Rab27a expression is listed from left to right, starting with the highest expression level. A high enrichment score indicates a positive correlation with Rab27a expression, and a low enrichment score indicates the reverse.
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pone-0089782-g006: Gene set variation analysis with Rab27a expression.Gene set variation analysis with Rab27a expression was analyzed using the GSVA package. Gene expression signatures of migration were generated from the GO list. Rab27a expression is listed from left to right, starting with the highest expression level. A high enrichment score indicates a positive correlation with Rab27a expression, and a low enrichment score indicates the reverse.

Mentions: As GO analysis showed that Rab27a expression was strongly associated with migration, we performed GSVA with Rab27a expression (Figure 6). The genes up- and down-regulated in migration correlated positively and negatively, respectively, with Rab27a expression in CGGA and the other 3 validation datasets.


Rab27a was identified as a prognostic biomaker by mRNA profiling, correlated with malignant progression and subtype preference in gliomas.

Wang H, Zhao Y, Zhang C, Li M, Jiang C, Li Y - PLoS ONE (2014)

Gene set variation analysis with Rab27a expression.Gene set variation analysis with Rab27a expression was analyzed using the GSVA package. Gene expression signatures of migration were generated from the GO list. Rab27a expression is listed from left to right, starting with the highest expression level. A high enrichment score indicates a positive correlation with Rab27a expression, and a low enrichment score indicates the reverse.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935941&req=5

pone-0089782-g006: Gene set variation analysis with Rab27a expression.Gene set variation analysis with Rab27a expression was analyzed using the GSVA package. Gene expression signatures of migration were generated from the GO list. Rab27a expression is listed from left to right, starting with the highest expression level. A high enrichment score indicates a positive correlation with Rab27a expression, and a low enrichment score indicates the reverse.
Mentions: As GO analysis showed that Rab27a expression was strongly associated with migration, we performed GSVA with Rab27a expression (Figure 6). The genes up- and down-regulated in migration correlated positively and negatively, respectively, with Rab27a expression in CGGA and the other 3 validation datasets.

Bottom Line: Mutations in this gene are associated with Griscelli syndrome type 2.Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration.The 3 validation datasets revealed similar findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

ABSTRACT

Purpose: Rab27a belongs to the Rab small GTPase superfamily. The protein is membrane-bound and may be involved in protein transport and small GTPase-mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. However, the prognostic and molecular features of gliomas with Rab27a expression are still unclear.

Experimental design: We used a whole-genome mRNA expression microarray dataset of 220 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set. In this set, 220 gliomas, consisting of 97 WHO Grade II gliomas, 34 WHO Grade III gliomas, and 89 WHO Grade IV gliomas, were analyzed using the Kaplan-Meier method. To validate the protein expression of Rab27a, we assayed another 162 glioma samples by immunohistochemistry. Three additional datasets were obtained as validation sets. Gene ontology (GO) analysis and gene set variation analysis (GSVA) were used for the functional annotation of Rab27a in 89 WHO Grade IV gliomas.

Results: Rab27a was significantly associated with grade progression and high mortality in all grades of glioma in the discovery set. Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration. The 3 validation datasets revealed similar findings. Rab27a was more highly expressed in gliomas than in normal brain tissues, and its expression increased with glioma grade progression.

Conclusions: Rab27a expression was significantly associated with grade progression and worse prognosis in all grades of gliomas, suggesting Rab27a as a novel biomarker with potentially important therapeutic implications.

Show MeSH
Related in: MedlinePlus