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

Dig Dis Sci. 2015 Aug;60(8):2477-87. doi: 10.1007/s10620-015-3648-2. Epub 2015 Apr 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • C-Reactive Protein / analysis
  • CD8-Positive T-Lymphocytes / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / surgery
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunochemistry
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Retrospective Studies

Substances

  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • C-Reactive Protein