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Systemic Analysis of Predictive Biomarkers for Recurrence in Colorectal Cancer Patients Treated with Curative Surgery

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Abstract

Background

Preoperative serum systemic inflammatory response (SIR) in patients with colorectal cancer (CRC) has been reported to be a predictive biomarker of early recurrence. The molecular status of CRC, including microsatellite instability (MSI), BRAF and KRAS mutations, and tumor-infiltrating lymphocytes (TILs), has also been associated with recurrence in CRC patients treated with curative surgery.

Aim

We investigated the impacts of SIR status, TILs, and MSI on recurrence in curative CRC patients.

Methods

In this retrospective study, we enrolled 157 patients with stage I–III CRC undergoing curative surgery, for whom preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and C-reactive protein (CRP) data were available as indicators of SIR status. Molecular status was evaluated by counting TILs as the numbers of intratumoral Foxp3- and CD8-positive T cells by immunohistochemistry. MSI status was determined using five mononucleotide repeat microsatellite markers.

Results

Kaplan–Meier analysis of SIR indicators revealed that higher CRP, NLR, and PLR were associated with significantly poorer disease-free survival (DFS). Low levels of infiltrating CD8-positive T cells in CRC tissue was a significant predictor of poor DFS. Multivariate analysis showed that few infiltrating CD8-positive T cells and high serum CRP levels were independent predictive factors for recurrence. Furthermore, the combination of high CRP and few infiltrating CD8-positive T cells increased the predictive accuracy in these patients.

Conclusions

The results of this study suggest that both CRP levels in preoperative serum and CD8 T cells in CRC tissue are useful biomarkers for predicting early relapse in CRC patients treated with curative surgery.

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Acknowledgments

This work was supported in part by a Grant in Aid for Scientific Research (21791280) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Conflict of interest

The authors have no conflicts of interests to disclose.

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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

    Koichiro Mori, Yuji Toiyama, Susumu Saigusa, Hiroyuki Fujikawa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Yasuhiro Inoue, Koji Tanaka, Yasuhiko Mohri & Masato Kusunoki

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  1. Koichiro Mori
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  2. Yuji Toiyama
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Correspondence to Yuji Toiyama.

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Mori, K., Toiyama, Y., Saigusa, S. et al. Systemic Analysis of Predictive Biomarkers for Recurrence in Colorectal Cancer Patients Treated with Curative Surgery. Dig Dis Sci 60, 2477–2487 (2015). https://doi.org/10.1007/s10620-015-3648-2

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  • DOI: https://doi.org/10.1007/s10620-015-3648-2

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