Analysis of preoperative serum cytokine levels in patients with oral squamous cell carcinoma

Abstract

This study investigates preoperative serum cytokine levels in patients with oral squamous cell carcinoma (OSCC). The study included 51 patients with OSCC and 42 healthy controls (HCs). Serum samples of 12 cytokines were analyzed using a multiplex bead-based flow cytometry immunoassay. Mann-Whitney U test and binary logistic regression analysis were performed to identify significant indicators of OSCC. Receiver operating characteristic (ROC) curves evaluated the diagnostic performance.Spearman analysis was assessed the correlation between cytokines and tumor-node-metastasis staging of OSCC. Serum levels of interleukin (IL)-2, IL-5, IL-6, IL-8, IL-12P70, IL-17, and interferon gamma (IFN-γ) were significantly higher (P < 0.05) in patients with OSCC than in HCs. IL-5, IL-6, IL-8, IL-12P70, IL-17, IFN-γ, combination 1 (IL-6 and IL-8), and combination 2 (IL-6 and IL-12P70) had area under the curve (AUC) values > 0.7, with combination 2 exhibited the highest AUC of 0.995. Serum cytokine profiles were significantly different (P < 0.05) between the patients with OSCC and HCs. IL-5, IL-6, IL-8, IL-12P70, IL-17, IFN-γ, combination 1, and combination 2 effectively distinguished between HCs and patients with OSCC. Cytokine combinations enhanced OSCC diagnostic accuracy, with significantly elevated IL-6 levels (P < 0.05) in advanced-stage compared to early-stage OSCC, indicating its potential impact on disease progression and prognosis.

Keywords: Cytokines; Inflammatory; Oral squamous cell carcinoma; Serum.

Fig. 1

Distribution of cytokine concentrations in the serum of healthy control (HC) and oral squamous cell carcinoma (OSCC) groups. Violin plots depict the concentration of each cytokine in the HC and OSCC groups. Statistical differences were assessed using the Mann–Whitney U test. (***P < 0.001; **P < 0.01; *P < 0.05; ns: P > 0.05).

Fig. 2

Heatmap of cytokine serum concentrations in the healthy control (HC) and oral squamous cell carcinoma (OSCC) groups. The heatmap displays the average concentration of seven cytokines showing significant differences between the two groups. Each row represents a cytokine, and each column represents a different group. Data were averaged within each group to facilitate comparison. The OSCC group had higher concentrations of these seven cytokines than the HC group.

Fig. 3

Forest plot of cytokine concentrations in the healthy control (HC) and oral squamous cell carcinoma (OSCC) groups. The forest plot displays the mean difference in cytokine concentrations between the HC and OSCC groups, along with their confidence intervals. Forest plots were analyzed using logistic regression models to determine effect sizes and confidence intervals. Each bar in the forest plot represents a cytokine, where the length of the bar indicates the point estimate of the effect size, and the confidence interval is represented by a line segment to account for heterogeneity across different data. The OSCC group consistently demonstrated higher concentrations of IL-2, IL-5, IL-6, IL-8, IL-12P70, IL-17, IFN-α, IFN-γ, combination 1, and combination 2 than the HC group.

Fig. 4

Receiver operating characteristic (ROC) curve for patients with oral squamous cell carcinoma: (A) IL-2, (B) IL-5, (C) IL-6, (D) IL-8, (E) IL-12P70, (F) IL-17, (G) IFN -α, (H) IFN -γ, (I) combination 1, and (J) combination 2. The diagonal line represents the reference line. The solid line represents the ROC curve for the cytokines.

Fig. 5

Correlation heatmap of serum cytokines with different oral squamous cell carcinoma (OSCC) tumor–node–metastasis (TNM) stages. The results demonstrate a significant positive correlation between IL-6 levels and TNM stage, with more elevated IL-6 levels observed in advanced-stage OSCC than in early-stage OSCC.