Overexpression of DIO1 is related to poor prognosis through regulating EMT and TAM infiltration in gastric carcinoma

Gastric cancer (GC) remains a prevalent and lethal malignancy, with high rates of invasion and metastasis. Deiodinase 1 (DIO1) demonstrates the potential for tumor proliferation and invasion across various cancers, including GC. Herein, we aimed to investigate the role of DIO1 in tumor progression and its clinical significance in GC. In this study, we included 135 tumor microarray specimens from GC patients at Zhongshan Hospital, 329 GC patients from the Cancer Genome Atlas , and 300 GC patients from the Asian Cancer Research Group . Analysis of these three independent cohorts revealed that elevated DIO1 levels function as an independent adverse prognostic factor in GC. In vitro and in vivo studies manifested that DIO1 promotes GC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through the WNT/β-catenin/Twist axis. Furthermore, DIO1 enhances CCL2 production, facilitating tumor-associated macrophage (TAM) chemotaxis. Functional assays confirmed that DIO1 knockdown suppresses GC progression while its overexpression exacerbates it. In conclusion, our findings indicated that DIO1 is a pivotal oncogene in GC, serving as a potential inferior prognostic marker and a promising therapeutic target for improving GC treatment outcomes.