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AIM Polycomb Group complexes are epigenetic repressors that silence tumor suppressive genes. Studies demonstrated that pharmacologic inhibition of Polycomb Group complexes with 3-deazaneplanocin A (DZNeP) induces cancer cell death by re-expressing silenced genes. Here we evaluate the prognostic significance of DZNeP target genes in gastric and breast cancer. Patients & methods/materials: The prognostic impact of a DZNeP-regulated gene signature was investigated using the KM Plotter and cBio Portal resources containing microarray data from tumor tissue. RESULTS We report that elevated expression of DZNeP targets is associated with poor clinical outcome in gastric and breast cancer. In gastric cancer, elevated expression of DZNeP signature is inversely correlated with decreased overall survival. In breast cancer, DZNeP signature predicted poor prognosis in HER2+ tumors but not in HER2- neoplasms. CONCLUSION These findings demonstrate that DZNeP target genes are not predictive of better but rather of poor clinical outcome in gastric and breast cancer.