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Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs).

Methods

The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification.

Results

The presence of expression of GREM1 (p = 0.016) and high MVD (p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD (p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas (p < 0.001).

Conclusions

GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs.

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Acknowledgments

This research was supported by Grants from Taipei Veterans General Hospital (101DHA0100657, 100DHA0100480, 100DHA0100489 and 101DHA0100653), Center of Excellence for Cancer Research at Taipei Veterans General Hospital (DOH100-TD-C-111-007), Taiwan Clinical Oncology Research Foundation, the National Science Council (NSC100-2627-B-010-005), and the Ministry of Education, Aim for the Top University Plan (National Yang-Ming University).

Conflict of interest

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Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong St., Taipei, 112, Taiwan

    Ming-Huang Chen, Yi-Chen Yeh, Peter Mu-Hsin Chang & Chi-Ying F. Huang

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

    Ming-Huang Chen, Cheng-Hwai Tzeng, Peter Mu-Hsin Chang & Chun-Yu Liu

  3. Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Chen Yeh

  4. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Ming Shyr & Shin-E Wang

  5. Genomics Research Center, Academia Sinica, 128 Academia Rd., Sec. 2, Nankang Dist., Taipei, 115, Taiwan

    Yi-Hua Jan & Michael Hsiao

  6. Department of Medicine, Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

    Yee Chao

  7. Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

    Yee Chao, Chung-Pin Li & Ming-Han Chen

  8. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chung-Pin Li

  9. Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 112, Taiwan

    Chi-Ying F. Huang

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  1. Ming-Huang Chen
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  2. Yi-Chen Yeh
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  3. Yi-Ming Shyr
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  4. Yi-Hua Jan
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  5. Yee Chao
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  6. Chung-Pin Li
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  7. Shin-E Wang
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  8. Cheng-Hwai Tzeng
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  9. Peter Mu-Hsin Chang
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  10. Chun-Yu Liu
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  11. Ming-Han Chen
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  12. Michael Hsiao
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  13. Chi-Ying F. Huang
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Corresponding authors

Correspondence to Michael Hsiao or Chi-Ying F. Huang.

Additional information

M.-H. Chen and Y.-C. Yeh contributed equally to this work.

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Supplementary Figure 1 and Table S1 (DOC 604 kb)

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Chen, MH., Yeh, YC., Shyr, YM. et al. Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors. J Gastroenterol 48, 101–108 (2013). https://doi.org/10.1007/s00535-012-0614-z

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  • DOI: https://doi.org/10.1007/s00535-012-0614-z

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