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

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Tumor Biology

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.

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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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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Foundation Medical Center, Tainan, Taiwan

    Ming-Jen Sheu & Ching-Yih Lin

  2. Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

    Ming-Jen Sheu

  3. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan

    Chien-Feng Li & Li-Jung Ma

  4. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

    Chien-Feng Li

  5. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Chien-Feng Li

  6. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chien-Feng Li

  7. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Ching-Yih Lin

  8. Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan

    Sung-Wei Lee

  9. Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan

    Li-Ching Lin

  10. Department of Pathology, Chi Mei Foundation Medical Center, Tainan, Taiwan

    Tzu-Ju Chen

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  1. Ming-Jen Sheu
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Correspondence to Chien-Feng Li or Li-Jung Ma.

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Sheu, MJ., Li, CF., Lin, CY. et al. Overexpression of ANXA1 confers independent negative prognostic impact in rectal cancers receiving concurrent chemoradiotherapy. Tumor Biol. 35, 7755–7763 (2014). https://doi.org/10.1007/s13277-014-2032-8

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  • DOI: https://doi.org/10.1007/s13277-014-2032-8

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