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Tumor Biology

, Volume 35, Issue 8, pp 7755–7763 | Cite as

Overexpression of ANXA1 confers independent negative prognostic impact in rectal cancers receiving concurrent chemoradiotherapy

  • Ming-Jen Sheu
  • Chien-Feng Li
  • Ching-Yih Lin
  • Sung-Wei Lee
  • Li-Ching Lin
  • Tzu-Ju Chen
  • Li-Jung Ma
Research Article

Abstract

Neoadjuvant concurrent chemoradiation therapy (CCRT) is an increasingly common therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcomes after CCRT. Annexin I (ANXA1), encoded by ANXA1, is a Ca2+/phospholipid-binding protein that mediates actin dynamics and cellular proliferation, as well as suggesting tumor aggressiveness and predicting therapeutic response in certain malignancies. However, expression of ANXA1 has never been reported in rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of ANXA1 expression in patients with rectal cancer following neoadjuvant CCRT. We identified ANXA1 as associated with resistance to CCRT through data mining from a published transcriptomic dataset. Its immunoexpression was retrospectively assessed using H scores on pre-treatment biopsies from 172 rectal cancer patients treated with neoadjuvant CCRT followed by curative surgery. Results were correlated with clinicopathological features, therapeutic response, tumor regression grade (TRG), and metastasis-free survival (MeFS), as well as local recurrent-free survival (LRFS) and disease-specific survival (DSS). High expression of ANXA1 was associated with advanced pre-treatment tumor status (T3, T4, p = 0.022), advanced pre-treatment nodal status (N1, N2, p = 0.004), advanced post-treatment tumor status (T3, T4, p < 0.001), advanced post-treatment nodal status (N1, N2, p = 0.001) and inferior TRG (p = 0.009). In addition, high expression of ANXA1 emerged as an adverse prognosticator for DSS (p < 0.0001), LRFS (p = 0.0001) and MeFS (p = 0.0004). Moreover, high expression of ANXA1 also remained independently prognostic of worse DSS (hazard ratio [HR] = 3.998; p = 0.007), LRFS (HR = 3.206; p = 0.028) and MeFS (HR = 3.075; p = 0.017). This study concludes that high expression of ANXA1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients treated with neoadjuvant CCRT.

Keywords

ANXA1 Rectal cancer CCRT 

Notes

Acknowledgments

This study is supported by Chi Mei Medical Center (CMFHR10303) and the Ministry of Health and Welfare (MOHW103-TD-B-111-05)

Conflict Of Interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ming-Jen Sheu
    • 1
    • 2
  • Chien-Feng Li
    • 3
    • 4
    • 5
    • 6
  • Ching-Yih Lin
    • 1
    • 7
  • Sung-Wei Lee
    • 8
  • Li-Ching Lin
    • 9
  • Tzu-Ju Chen
    • 10
  • Li-Jung Ma
    • 3
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineChi Mei Foundation Medical CenterTainanTaiwan
  2. 2.Department of Medicinal ChemistryChia Nan University of Pharmacy and ScienceTainanTaiwan
  3. 3.Department of PathologyChi Mei Medical CenterTainanTaiwan
  4. 4.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  5. 5.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan
  6. 6.Institute of Clinical MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  7. 7.Department of Leisure, Recreation, and Tourism ManagementSouthern Taiwan University of Science and TechnologyTainanTaiwan
  8. 8.Department of Radiation OncologyChi Mei Medical CenterTainanTaiwan
  9. 9.Department of Radiation OncologyChi Mei Medical CenterTainanTaiwan
  10. 10.Department of PathologyChi Mei Foundation Medical CenterTainanTaiwan

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