Serum Systemic Inflammatory Response Research Articles

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

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

Comprehensive analysis of predictive biomarkers for patients with curative colorectal cancer patients and high risk of recurrence.

607 Background: Preoperative serum systemic inflammatory response (SIR) has been reported in patients with various cancers including colorectal cancer (CRC) as predictive biomarker of early recurrence. Molecular phenotypes of CRC including microsatellite instability (MSI) status and tumor infiltrating lymphocytes (TILs) have also known to be associated with recurrence in curative CRC patients. We comprehensively evaluated SIR status, MSI status and TILs in curative CRC patients and investigated which can be promising as high risk markers of recurrence in these patients. Methods: This retrospective study enrolled 157 CRC patients with stage I-III undergoing curative operation for whom preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and CRP were available as indicators of SIR status. For analysis of molecular phenotypes, we evaluated TILs by counting the number of intra-tumor Foxp3 and CD8 positive T cells by IHC analysis. Next, MSI status was determined in using 5 mononucleotide repeat microsatellite markers. Finally, we investigated the impact of SIR status, TILs and MSI status on the recurrence of these patients. Results: This study included a total of 90 males and 67 females, with an average age of 66.9 years. Twenty-nine patients (18.4%) developed recurrence. Kaplan-Meier analysis using SIR indicators revealed that patients with high CRP, NLR and PLR levels were significantly poorer disease free survival (DFS) than those with low levels. Low infiltrating CD8-positive T cells were significantly predictive factors for poor DFS, but there was no correlation between MSI status and recurrence, In univariate analysis, low infiltrating CD8-positive T cells, high CEA, CRP, NLR and PLR levels in serum were significantly predictive factors for poor DFS, respectively. Multivariate analysis showed that low infiltrating CD8-positive T cells and high serum CRP levels were independent predictive markers for recurrence in curative CRC patients. Conclusions: We demonstrated that evaluation of both CRP levels in preoperative serum and tumor infiltrating CD8 lymphocytes in CRC tissues are useful to predict the curative CRC patients with early relapse.