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|a Background: Gastric cancer (GC) is one of the leading malignant diseases worldwide, especially in Asia. CAST is a potential oncogene in GC carcinogenesis. The character of macrophage infiltration in the GC microenvironment also remains unaddressed. Methods: We first applied machine searching to evaluate gene candidates for GC. CAST expression and pan-cancer surveyance were analyzed using the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. The protein–protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using a Kaplan–Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC were determined using TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkages between genes. Results: After the machine-assisted search, CAST expression was found to significantly influence the overall survival of GC patients. STRING revealed CAST-related proteomic and transcriptomic associations, mainly concerning the CAPN family. Moreover, CAST significantly impacts the prognosis of GC based on the validation of other datasets. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; log-rank P = 9.4 × 10−8 ). CAST and Lgr5 expression were both positively correlated with WNT 2 and WNT 2B. Among the GC patients in several datasets, CAST and macrophage infiltration, evaluated together, showed no obvious association with poor clinical overall survival. Conclusions: CAST plays an important role in the clinical prognosis of GC and is associated with WNT 2/WNT 2B/Lgr5. Our study demonstrates that CAST’s influence on overall survival in GC is regulated by macrophage infiltration. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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