The expression of SOCS1 and TLR4-NFkappaB pathway molecules in neoplastic cells as potential biomarker for the aggressive tumor phenotype in laryngeal carcinoma.

Abstract

Suppressor of cytokine signaling 1 (SOCS1) is the key regulator of cytokine-mediated innate and adaptive immunity. One of the molecular mechanisms of SOCS1 is connected with inhibition of TLR4-NFκB pathway. The relationships among these molecules in laryngeal carcinoma are not exactly known. In this preliminary study we focused on their special activity and role in regulation of development and progression of laryngeal carcinoma. To investigate NFκB (p65 subunit) nuclear and cytoplasmic expression in 45 tumor samples of advanced laryngeal carcinoma IHC staining was performed. To determine the mRNA expression levels of TLR4, IRAK1, TRAF6 and SOCS1 in isolated neoplasm cells and non-cancerous adjacent mucosa epithelial cells RT-PCR was used. The invasiveness of laryngeal carcinomas was evaluated according to tumor front grading, TFG, which included tumor-related features (cytoplasmic differentiation, nuclear polymorphism, number of mitoses) and adjacent stroma-related characteristics of the peripheral edge of tumor infiltration (mode of infiltration, depth of invasion and plasmalymphocytic infiltration). The relationships between pT, pN status, the histological G grade, certain clinicopathological characteristics as well as postoperative observation time and the mRNA expression of the molecules mentioned earlier were investigated. Significant differences of TLR4-NFκB pathway molecules and SOCS1 mRNA expression in laryngeal tumor cells and normal adjacent mucosa cells as well as significant interconnections of TLR4, SOCS1 and NFκB(p65) in isolated tumor cells were obtained. This preliminary study demonstrated that the expression of SOCS1 and TLR4-NFκB pathway molecules had a strong association with the aggressiveness of laryngeal carcinoma. Positive relationships of TRAF6 in tumor margin cells with the histological grade and the mode of tumor invasion as well as the TFG total score were highlighted. Significant positive correlations were found between the TLR4 in tumor central cells and the TFG total score. Negative relationships of SOCS1 in tumor central cells with the histological grade were also noted. Significant positive correlations were found between the cytoplasmic NFκB(p65) and the mode of invasion as well as TFG total score. Our findings confirmed the importance of SOCS1 and TLR4-NFκB pathway molecules as potential biomarkers for assessment of the aggressive tumor phenotype in laryngeal carcinoma.Key words: laryngeal carcinoma, SOCS1 (suppressor of cytokine signaling 1), TLR4 (toll-like receptor 4), IRAK1 (interleukin -1 receptor -associated kinase), TRAF6 (TNF receptor-associated factor 6), NFκB (nuclear factor kappa B, p65 subunit), TFG (tumor front grading)

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