Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer

Abstract

The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan-Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46-0.88), 0.74 (95% CI: 0.56-0.86), and 0.79 (95% CI: 0.75-0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42-2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76-5.01, P < 0.001). The synthesized Kaplan-Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival. The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).

FIGURE 1

Flow diagram of study selection process.

FIGURE 2

The ROC and sROC curve for the diagnostic analysis. (A) The AUC value of IL-6 in CRC from the original study. (B) Summary receiver operating characteristic curves for IL-6 in the diagnosis of CRC. (C) The AUC value of IL-6 in CRC from IPD meta-analysis. (D) Forest plots of sensitivities and specificities of serum IL-6 in the diagnosis of CRC. AUC = area under curve, CRC = colorectal cancer, IPD = individual participant data, ROC = summary receiver-operating characteristic, sROC = summarize in receiver-operating characteristic curves.

FIGURE 3

Results of prognostic analysis for serum IL-6 in CRC. (A) Forest plot of studies evaluating serum IL-6 level for CRC OS. (B) Forest plot of studies evaluating serum IL-6 level for CRC DFS. (C) Reconstructed Kaplan–Meier survival estimates of OS by secondary analysis of survival data. (D) Reconstructed Kaplan–Meier survival estimates of DFS by secondary analysis of survival data. CRC = colorectal cancer, DFS = disease-free survival, OS = overall survival.