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Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer

Tumor Biology volume 37, pages 3571–3580 (2016)Cite this article

Abstract

We evaluated the clinical influence of cancer stem cells (CSCs) on residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were assessed. To identify CSCs, immunohistochemistry was performed using their surrogate makers (CD44 and aldehyde dehydrogenase 1 [ALDH1]) in full section tissues. Of the 145 cases, ALDH1 and CD44 positivity was found in 80.0 % (n = 116) and 47.6 % (n = 69), respectively; ALDH1 positivity showed weakly positive correlation with CD44 (r s  = 0.269, P = 0.002). ALDH1 and CD44 positivity was related to lower tumor regression grade (TRG) (P = 0.009 and 0.003, respectively). Additionally, ALDH1 positivity was associated with positive circumferential resection margin (P = 0.019). However, ALDH1 and CD44 positivity showed no relationship with KRAS or BRAF mutation. In univariate analysis, ALDH1 positivity was associated with short recurrence-free survival (RFS) (P = 0.005) and rectal cancer-specific survival (RCSS) (P = 0.043), but not CD44 positivity (RFS, P = 0.725; RCSS, P = 0.280). In multivariate analysis, ALDH1 positivity was an independent prognostic factor for poor RFS (P = 0.039; hazard ratio = 2.997; 95 % confidence interval = 1.059–8.478), but not RCSS (P = 0.571). The expression of ALDH1 assessment independently predicts RFS in patients with residual disease after CRT. These results suggest that targeting CSCs could be an effective therapeutic approach to rectal cancer patients receiving preoperative CRT.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (grant number: NRF-2015R1C1A1A02037597).

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Authors and Affiliations

  1. Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, South Korea

    Ghilsuk Yoon, Sol-Min Kim & An Na Seo

  2. Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, South Korea

    Hye Jin Kim

  3. Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, South Korea

    An Na Seo

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Figure S1

Prognostic values of ALDH1 on residual rectal cancer after preoperative CRT. Kaplan-Meier estimates of rectal cancer specific survival (A) for patients with downstaging and (B) for patients without downstaging. (GIF 9 kb)

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Yoon, G., Kim, SM., Kim, H.J. et al. Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer. Tumor Biol. 37, 3571–3580 (2016). https://doi.org/10.1007/s13277-015-4201-9

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  • DOI: https://doi.org/10.1007/s13277-015-4201-9

Keywords

  • Rectal cancer
  • Preoperative chemoradiotherapy
  • Aldehyde dehydrogenase 1
  • CD44