title: Systemic Analysis of Predictive Biomarkers for Recurrence in Colorectal Cancer Patients Treated with Curative Surgery.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, koichiromori@clin.medic.mie-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Mori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.forename: Minako
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Araki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007120:Immunochemistry; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D002097:C-Reactive Protein
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