Abstract
BackgroundThe interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis.MethodsA total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis).ResultsIncreases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (P < 0.001, P = 0.001), LN metastasis (P < 0.001, P = 0.024) and TNM stage (P < 0.001, P < 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (P = 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; P < 0.001) and overall survival (OS; P = 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (r2 = 0.049, P = 0.018).ConclusionPreoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.
Highlights
The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy
Recent studies have demonstrated that the hypermethylation of Suppressor of cytokine signaling-1 (SOCS-1) is not controlled by the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, and IL-6 cannot perform a role in cancer defense; on the contrary, it is involved in cancer development [3,6]
Patients' characteristics The patients were classified by their pathologic characteristics, including tumor size, depth of tumor invasion, status of lymph node metastasis, TNM staging, and peritoneal metastasis
Summary
The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. IL-6 is generally known to be involved in host defense mechanisms. Suppressor of cytokine signaling-1 (SOCS-1) is one of the STAT-activated genes, which is upregulated by IL-6 and is involved in the downregulation of the JAK/STAT pathway [3,4,5]. Recent studies have demonstrated that the hypermethylation of SOCS-1 is not controlled by the JAK/STAT pathway, and IL-6 cannot perform a role in cancer defense; on the contrary, it is involved in cancer development [3,6]
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