Clinical Roles of Interleukin-6 and STAT3 in Oral Squamous Cell Carcinoma

Abstract

The effect inflammation has on cancer prognosis is marked by the presence of cytokines and chemokines. Interleukin-6 (IL-6) is one a multifunctional cytokine that regulates inflammatory responses. We investigated the roles of IL-6 and STAT3 and examined the relationship between IL-6 signaling and clinicopathological factors in patients with oral squamous cell carcinoma (OSCC). We retrospectively examined 116 patients who underwent radical surgery for OSCC. IL-6 and STAT3 expression were detected by immunohistochemistry. IL-6 and STAT3 positivity were detected by IHC, at 78.4 and 80.2 %, respectively. IL-6 expression was significantly associated with pattern of invasion (P = 0.004), vascular invasion (P = 0.003), and pathological nodal status (P = 0.019). Multivariate logistic regression analysis revealed that IL-6 expression was significantly associated with vascular invasion (P = 0.044). Meanwhile, there was no significant association between STAT3 expression and clinicopathological factors and no significant relationship between IL-6 and STAT3 expression. IL-6 expression was significantly associated with 5-year disease-free survival. These results suggest that IL-6 is involved in lymphangiogenesis and recurrence in OSCC.

Inflammation related genes are upregulated in surgical margins of advanced stage oral squamous cell carcinoma

“…22 Further, IL6 expression correlated with pattern of invasion, vascular invasion and pathological nodal status.25 IL6 overexpression led to the decrease of disease free survival rate in OSCC patients. 25 It has been shown that SOCS3 polymorphisms was linked with the risk of head and neck squamous cell carcinoma.26 Upregulation of SOCS3 was observed in OSCC compared with the control.27 SPRY1 is a modulator of a receptor tyrosine kinase signaling. Though, role in OSCC has not yet been reported.…”

Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma

“…Gas6 decreased IL‐2 during invasion, possibly clarifying a role for IL‐2 during cancer progression generally. IL‐6 is a cytokine involved in the regulation of immune responses associated with tumor development including OSCC . Interestingly, IL‐6 in OSCC is associated with tumor invasion, but it was only present in cancer cell membranes.…”

“…IL-6 is a cytokine involved in the regulation of immune responses associated with tumor development including OSCC. 27 Interestingly, IL-6 in OSCC is associated with tumor invasion, but it was only present in cancer cell membranes. In our studies, we observed a significant decrease in IL-6 in the Gas6-treated cells.…”

CD109 and squamous cell carcinoma

“…Oral squamous cell carcinoma (OSCC) accounts for 2–3% of all cancers worldwide [ 37 ]. Loss of function mutation in TGF-β type II receptor is a frequent event for oral cavity SCC [ 2 ].…”

“…Signal transducer and activator of transcription factor 3 (STAT3) is critical to cell proliferation, differentiation, migration, survival, and oncogenesis [ 37 , 55 ]. Litvinov et al [ 56 ] reported that the expression of CD109 protein was markedly decreased in psoriatic epidermis as compared to adjacent uninvolved skin.…”