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Inflammatory levels correlate with PANoptosis and cGAS-STING pathway activation in colorectal serrated lesions

Year: 2026

Type: article

Abstract: Colorectal serrated lesions (CSL) are linked to colorectal cancer development, but the interplay between inflammatory responses, PANoptosis, and cGAS-STING pathway activation in their pathogenesis remains unclear. This study aimed to explore correlations between these factors in CSL. A comparative study was conducted involving 72 patients with CSL and 20 healthy controls. Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory factors in peripheral blood, including various cytokines such as IL-1β and IL-6. In terms of sample selection, tissue samples were taken from CSL patients, including lesion tissues from three subgroups of patients: HP, SSL, and TSA, while a control group was set up to collect normal intestinal mucosal tissue. Expression of cGAS-STING pathway molecules (cGAS, STING) and PANoptosis-related proteins (MLKL, NLRP3, caspase-3) in tissues was analyzed using immunofluorescence (IF) and Western blot (WB). Clinical inflammatory indices (hsCRP, white blood cell count, SII, PIV) were also compared. Baseline characteristics were comparable between CSL groups and healthy control group. CSL patients showed significantly elevated inflammatory markers (hsCRP, WBC, SII, PIV; all P < 0.001) and peripheral cytokines (IL-1β, IL-6, IL-8, TNF-α, IL-10, IFNβ; all P < 0.001), indicating systemic inflammation in CSL pathogenesis. IF and WB analyses confirmed that the expression levels of cGAS, STING, MLKL, NLRP3, and caspase-3 were significantly upregulated in lesion tissues of CSL patients (HP, SSL, TSA subgroups) compared with normal intestinal mucosa of healthy controls (all P < 0.001). Inflammatory levels, cGAS-STING pathway activation, and abnormal PANoptosis are associated in CSL, providing experimental evidence for its pathogenesis and potential combined biomarkers for clinical evaluation.

Source: Journal of Radiation Research and Applied Sciences

DOI: 10.1016/j.jrras.2026.102208