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Ann Surg Oncol. 2012 Oct;19(11):3491-9. doi: 10.1245/s10434-012-2389-0. Epub 2012 May 17.

Integrating bioinformatics and clinicopathological research of gastrointestinal stromal tumors: identification of aurora kinase A as a poor risk marker.

Author information

  • 1Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. ccyen@vghtpe.gov.tw

Abstract

BACKGROUND:

For completely resected primary gastrointestinal stromal tumors (GISTs), mitotic rate, tumor size, and tumor location are important risk factors for recurrence. However, molecular markers for recurrence are still lacking.

METHODS:

We reanalyzed GIST gene expression profile GSE8167 available from the Gene Expression Omnibus (GEO) and confirmed the prognostic influence of one selected gene, aurora kinase A (AURKA), in another cohort of 142 patients using immunohistochemistry (IHC).

RESULTS:

Thirty-two cases in GSE8167 were classified into two risk groups with distinct recurrence-free survival (RFS) and expression profiles using modified criteria of Miettinen et al. from the Armed Forces Institute of Pathology (AFIP-Miettinen). AURKA was among the 19 genes common to the top 50 features of the high-risk phenotype and a 67-gene signature called the complexity index in sarcomas. AURKA was significantly overexpressed in the high-risk group, and patients with high AURKA expression had significantly worse RFS than those with low expression. In the IHC-validated cohort, AURKA expression was significantly higher in nongastric tumors than in gastric tumors and was significantly correlated with AFIP-Miettinen risk group. Univariate analysis showed that RFS was significantly influenced by tumor size, mitotic count, AFIP-Miettinen risk group classification, and AURKA expression. However, only tumor size (P = 0.017), mitotic count (P = 0.007), and AURKA expression (P = 0.039) were identified as independent unfavorable prognostic factors for RFS in multivariate analysis.

CONCLUSIONS:

By integrating bioinformatics and clinicopathological studies, AURKA was identified as a marker for high-risk GIST.

PMID:
22588468
[PubMed - indexed for MEDLINE]
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