TY - JOUR
T1 - Systemic Analysis of Predictive Biomarkers for Recurrence in Colorectal Cancer Patients Treated with Curative Surgery
AU - Mori, Koichiro
AU - Toiyama, Yuji
AU - Saigusa, Susumu
AU - Fujikawa, Hiroyuki
AU - Hiro, Junichiro
AU - Kobayashi, Minako
AU - Ohi, Masaki
AU - Araki, Toshimitsu
AU - Inoue, Yasuhiro
AU - Tanaka, Koji
AU - Mohri, Yasuhiko
AU - Kusunoki, Masato
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/8/23
Y1 - 2015/8/23
N2 - 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.
AB - 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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U2 - 10.1007/s10620-015-3648-2
DO - 10.1007/s10620-015-3648-2
M3 - Article
C2 - 25840921
AN - SCOPUS:84937519210
SN - 0163-2116
VL - 60
SP - 2477
EP - 2487
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 8
ER -