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Significant correlation between LKB1 and LGR5 gene expression and the association with poor recurrence-free survival in rectal cancer after preoperative chemoradiotherapy

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Abstract

Purpose

The aim of the present study was to investigate whether the gene expression levels of LKB1 and LGR5 correlated with clinical outcome in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy (CRT).

Methods

Residual cancer cells were obtained from 52 patients with locally advanced rectal cancer treated with preoperative CRT. Total RNA was then isolated from formalin-fixed, paraffin-embedded specimens using microdissection. The expression levels of LKB1 and LGR5 genes were measured using real-time reverse-transcription polymerase chain reaction and by immunohistochemistry. In addition, in vitro studies were performed using colon cancer cell lines to study the serial changes of LKB1, LGR5 and PRKAA1 (AMPK) gene expression levels after irradiation.

Results

Our data demonstrate that specimens obtained from patients with poor pathological response and tumor recurrence had significantly higher gene expression levels of LKB1 and LGR5 than those without them (P < 0.05), and there was a significant positive correlation between LKB1 and LGR5 gene expression after CRT (Spearman’s ρ: 0.429, P = 0.0023). The patients with high expression levels of both LKB1 and LGR5 had a significantly lower recurrence-free survival compared with the other group (P = 0.0055, 95 % confidence interval: 1.39–11.08). Lastly, in vitro studies demonstrated a similar pattern of serial gene expression among LKB1, LGR5 and PRKAA1 after irradiation.

Conclusions

Our results suggest that LKB1 and LGR5 expression may be implicated in resistance to CRT, therefore contributing to tumor relapse in patients with locally advanced rectal cancer treated with preoperative CRT.

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Acknowledgments

The authors would like to thank Motoko Ueeda and Yuka Kato for providing excellent technical assistance.

Conflict of interest

Susumu Saigusa and other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Susumu Saigusa, Yasuhiro Inoue, Koji Tanaka, Yuji Toiyama, Mikio Kawamura, Yoshinaga Okugawa, Masato Okigami, Junichiro Hiro, Keiichi Uchida, Yasuhiko Mohri & Masato Kusunoki

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  1. Susumu Saigusa
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  2. Yasuhiro Inoue
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  3. Koji Tanaka
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Correspondence to Susumu Saigusa.

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Saigusa, S., Inoue, Y., Tanaka, K. et al. Significant correlation between LKB1 and LGR5 gene expression and the association with poor recurrence-free survival in rectal cancer after preoperative chemoradiotherapy. J Cancer Res Clin Oncol 139, 131–138 (2013). https://doi.org/10.1007/s00432-012-1308-x

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  • DOI: https://doi.org/10.1007/s00432-012-1308-x

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