Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer patients

Abstract

It has been suggested that interleukin 6 (IL-6) plays a potential role in the growth and progression of tumors, including esophageal cancer (EC). The aim of the study was to compare clinical significance of serum IL-6 with classic tumor markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) - in EC patients in relation to its histological types - squamous cell carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The diagnostic criteria and prognostic values for markers were defined. The levels of all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The percentage of elevated results was substantially higher for IL-6 (86%) than for CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on distant metastases and patients' survival in EC and were significantly higher in ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area under receiver operating characteristic curve (0.92) was larger than for CEA (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91, 0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than classic tumor markers in the diagnosis of EC, especially in patients with ESCC.

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

“…IL-6 is activated in response to reflux and the IL-6/STAT3 antiapoptotic pathway may underlie the development of dysplasia and tumor (85). Serum IL-6 levels were reported to provide 87% sensitivity and 92% specificity for EAC diagnosis in a recent retrospective study (86). However, the study only compared between healthy and EAC groups.…”

The tumor microenvironment in esophageal cancer

“…Also, in the L2-IL-1β mouse model of BE/EAC, exposure to bile acids accelerated development of BE and EAC by an IL-6 dependent mechanism, with failure of carcinogenesis in the setting of IL-6 deficiency 15 . In addition, patients with EAC had higher serum levels of IL-6 than normal controls 52 , and increased serum IL-6 was associated with progression from BE to EAC 53 . IL-6 is also one of the primary inflammatory mediators produced by adipose tissue and thus may be important in obesity-related inflammation 54 .…”

Serum concentrations of receptor for interleukin 8 in patients with esophageal cancer

“…The univariate log -rank analysis indicated that the histological type of EC (P = 0.017), tumor studies, where serum levels of other inflammatory proteins such as CXCL -12 and its receptor (CXCR -4), CRP, and IL -6 were also significantly higher in EC patients in comparison with controls. [11][12][13] Other authors have revealed that CXCR -2 expression is significantly higher in patients with EC than in healthy individuals. However, these results were obtained using the immunohistochemical method.…”

“…The cut -off value of CXCR -2 levels was estimated using the Youden index as 0.72 ng/ml, while for the classic tumor markers (SCC -Ag, 2 ng/ml; CEA, 4 ng/ml) and CRP (5.75 mg/l), the cut -off values were previously established in our department based on the 95th percentile. [11][12][13] DISCUSSION Chemokines and their specific receptors play an important role in tumor growth, angiogenesis, invasion, and metastasis of several malignancies, including EC. The CXCR2 is a member of the G -protein -coupled receptor family.…”