The Prognostic Role of IL-6 and RBP4 in Colorectal Cancer

<b>Background/Objectives:</b> Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Inflammation and metabolic dysregulation, particularly those related to obesity, have emerged as critical contributors to CRC progression. Interleukin-6 (IL-6) and retinol-binding protein 4 (RBP4), an adipokine involved in metabolic regulation, may be key mediators of these processes. This study aimed to evaluate the expression levels of IL-6 and RBP4 in CRC tissues and their associations with clinicopathological features and overall survival. Furthermore, in silico analyses were performed to explore the molecular networks and signaling pathways related to both biomarkers. <b>Methods:</b> Immunohistochemical staining of IL-6 and RBP4 was conducted in 118 CRC and matched adjacent normal tissues. Expression levels were assessed using the H-score system and correlated with clinical parameters. Survival analysis was performed using Kaplan-Meier curves. In silico analyses were based on RNA-seq data from TCGA and included pathway enrichment, gene co-expression, and protein-protein interaction networks. <b>Results:</b> IL-6 and RBP4 expression were significantly elevated in tumor tissue compared to adjacent normal mucosa. High IL-6 expression correlated with age and obesity measures, while RBP4 expression showed significant associations with pT stage, lymph node involvement, TNM stage, and obesity-related parameters. Kaplan-Meier analyses indicated shorter overall survival in patients with high IL-6 or RBP4 expression. In silico analysis confirmed upregulation of IL6 and RBP4 in CRC and highlighted immune-related pathways for IL-6 and developmental signaling for RBP4. <b>Conclusions:</b> Elevated expression of IL-6 and RBP4 in CRC tissue is associated with adverse clinical features and reduced survival, underscoring their potential role as prognostic biomarkers. These findings support the involvement of inflammation and metabolic dysfunction in CRC progression and suggest IL-6 and RBP4 as candidates for future targeted therapeutic approaches.