Abstract

BackgroundThe purpose of the study was to assess the significance of the local cytokine composition in patients with esophageal squamous cell carcinoma (EC) for the disease prognosis. MethodsCytokines were studied in tumor, peritumoral (PT) and resection line (RL) tissues of 36 patients with stage II-III EC. All patients received surgery; further treatment depended on the tumor stage. During the observation, patients were divided into groups with short and prolonged progression-free survival (< and >1.5 years). Levels of TNF-α, IL-1b, IL-6, IL-8, and IL-10 were determined in tissue homogenates by ELISA and calculated in pg/mL/g of protein. Discriminant and ROC analyses were performed with the calculation of the area under a ROC curve (AUC) and cut-off points for statistically significant indicators sharing with maximum diagnostic sensitivity (DSe) and specificity (DSp) two alternative signs: the presence or absence of the risk of early progression. ResultsPatients showed different initial levels of tissue pro-and anti-inflammatory cytokines. PT of patients with the further progression was characterized by higher levels of TNF-α (by 1.9) and IL-10 (by 1.6 times), and their tumor tissues – by 2.1 times higher IL-1b and 1.6 times higher IL-8 (p<0.05). The ROC analysis demonstrated the following cut-off values: in tumors 57.5pg/mL/g (IL-1b) and 4.5pg/mL/g (IL-10), in PT 36.0pg/mL/g (IL-8) and 7.4pg/mL/g (TNF-α), in RL 9.8pg/mL/g (TNF-α) and 5.2pg/mL/g (IL-10). Exceeding them involved the risk of early disease progression. Levels of TNF-α in PT, IL-10 in tumors and RL showed good (AUC 0.8-0.9), and levels of TNF-α in RL, IL-1b in tumors and IL-8 in PT - satisfactory (AUC 0.7-0.8) ability to recognize the risk of early EC progression, p<0.005. ConclusionsEvaluation of local levels of cytokines allowed identifying the risk criteria for the development of early progression of EC, which along with clinical signs (the process spread) determine its prognosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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