title: 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).
authors.affiliation: From the Second Affiliated Hospital, Zhejiang University School of Medicine, (JX, YY, PL, HW); Department of Toxicology, Zhejiang University School of Public Health, (JX, YY, DX, YW); Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China (HZ); Department of Biochemical Diagnostics, Medical University of Bialystok, Sklodowska-Curie 24A, Bialystok, Poland (MS); Department of Pathology, University of Oulu, POB 5000, Oulu, Finland (MJM); Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine (PL); and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (JY).
authors.forename: Jinming
authors.initials: J
authors.lastname: Xu
authors.forename: Yao
authors.initials: Y
authors.lastname: Ye
authors.forename: Honghe
authors.initials: H
authors.lastname: Zhang
authors.forename: Maciej
authors.initials: M
authors.lastname: Szmitkowski
authors.forename: M J
authors.initials: MJ
authors.lastname: Mäkinen
authors.forename: Peiwei
authors.initials: P
authors.lastname: Li
authors.forename: Dajing
authors.initials: D
authors.lastname: Xia
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Wu
authors.forename: Han
authors.initials: H
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6