Decoding intratumoral cyclooxygenase-2 signaling through multi-omics: insights from esophageal cancer and beyond.

Cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis, was significantly upregulated in various cancers, including esophageal cancer (ESCA). This study investigated the role of COX-2 in cancer progression and its potential as a therapeutic target, utilizing multi-omics approaches, including single-cell RNA sequencing, spatial transcriptomics, protein docking analysis and experimental validation. We found that COX-2 expression was significantly elevated in ESCA and other cancers, correlating with malignant phenotype and poor prognosis. Enrichment analyses revealed that COX-2 was involved in key oncogenic signaling pathways, including TNF/NF-κB and IL-17, which promoted cell proliferation, migration, and invasion. Additionally, COX-2 facilitated a pro-inflammatory microenvironment by enhancing immune cell infiltration, particularly macrophages, monocytes, and mast cells. Functional assays demonstrated that celecoxib, a selective COX-2 inhibitor, effectively reduced ESCA cell proliferation, migration, and invasion in a dose-dependent manner. Pan-cancer analysis confirmed that COX-2 was a poor prognostic indicator across various cancers, highlighting its broader clinical relevance. This study underscored COX-2 as a critical regulator of inflammatory microenvironment and cancer progression in ESCA, supporting its potential as both a prognostic biomarker and therapeutic target. The use of COX-2 inhibitors, such as celecoxib, holds promise for improving patient outcomes in ESCA and other COX-2-associated cancers.