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Integrating Bioinformatics and Clinicopathological Research of Gastrointestinal Stromal Tumors: Identification of Aurora Kinase A as a Poor Risk Marker

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

This work was supported by grants from the Department of Health in Taiwan (Center of Excellence for Cancer Research at Taipei Veterans General Hospital, grant numbers DOH99-TD-C-111-007 and DOH100-TD-C-111-007, and the National Research Program for Biopharmaceuticals, grant number DOH100-TD-PB-111-TM026) and the National Science Council of Taiwan (grant number NSC 100-2314-B-075-081). This work also was partially supported by the Taiwan Clinical Oncology Research Foundation.

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chueh-Chuan Yen MD, PhD, Ting-Wei Chang MSc, Cheng-Hwai Tzeng MD & Ta-Chung Chao MD

  2. Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei, Taiwan

    Chueh-Chuan Yen MD, PhD, Ting-Wei Chang MSc, Cheng-Hwai Tzeng MD & Ta-Chung Chao MD

  3. National Yang-Ming University School of Medicine, Taipei, Taiwan

    Chueh-Chuan Yen MD, PhD, Cheng-Hwai Tzeng MD & Ta-Chung Chao MD

  4. Department of Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital and University, Gueishan Township, Taoyuan County, Taiwan

    Chun-Nan Yeh MD, Chi-Tung Cheng MD & Yi-Yin Jan MD, FACS

  5. Department of Pathology, Chang Gung Memorial Hospital and University, Gueishan Township, Taoyuan County, Taiwan

    Shih-Ming Jung MD & Shih-Chiang Huang MD

  6. Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Yeng-Yang Chen MD

  7. Department of Surgery, National Taiwan University Hospital, and National Taiwan University College of Medicine, Taipei, Taiwan

    Ching-Yao Yang MD

  8. Division of Hematology and Oncology, Tri-Service General Hospital, Taipei, Taiwan

    Ching-Liang Ho MD

  9. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Jonathan A. Fletcher MD

Authors
  1. Chueh-Chuan Yen MD, PhD
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  2. Chun-Nan Yeh MD
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  3. Chi-Tung Cheng MD
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  4. Shih-Ming Jung MD
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  5. Shih-Chiang Huang MD
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  6. Ting-Wei Chang MSc
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  7. Yi-Yin Jan MD, FACS
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  8. Cheng-Hwai Tzeng MD
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  9. Ta-Chung Chao MD
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  10. Yeng-Yang Chen MD
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  11. Ching-Yao Yang MD
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  12. Ching-Liang Ho MD
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  13. Jonathan A. Fletcher MD
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Corresponding authors

Correspondence to Chueh-Chuan Yen MD, PhD or Jonathan A. Fletcher MD.

Additional information

Chueh-Chuan Yen and Chun-Nan Yeh contributed equally to this study.

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Yen, CC., Yeh, CN., Cheng, CT. et al. Integrating Bioinformatics and Clinicopathological Research of Gastrointestinal Stromal Tumors: Identification of Aurora Kinase A as a Poor Risk Marker. Ann Surg Oncol 19, 3491–3499 (2012). https://doi.org/10.1245/s10434-012-2389-0

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  • DOI: https://doi.org/10.1245/s10434-012-2389-0

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