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The aim of the present study was to investigate the genetic signatures of cadmium-transformed prostate epithelial (CTPE) cells and to identify the potential molecular signaling involved in their malignant transformation. The dataset contained normal prostate epithelial (RWPE-1) and CTPE cells. To further examine the biological functions of the identified differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway enrichment analyses were performed. In total, 2357 DEGs were identified, including 1083 upregulated genes and 1274 downregulated genes. GO, KEGG, and Reactome pathway enrichment analyses indicated that upregulated genes were significantly enriched in ECM-receptor, focal adhesion, TGFβ signaling, and syndecan interactions, while downregulated genes were mainly involved in cell cycle regulation, arachidonic acid metabolism, oxidative phosphorylation, and folate biosynthesis (p <.05). The top upregulated (SATB1 (p <.0001), EYA2 (p <.0001) and KPNA7 (p <.0027)) and downregulated (PITX2 (p <.0007), PDLIM4 (p <.0020) and FABP5 (p <.0007)) genes were further validated via qRT-PCR analysis. In conclusion, the present study profiled DEGs in RWPE-1 and CTPE cells and identified gene pathways that may be associated with malignant transformation and tumor progression. • TGFβ, RAS and ECM-related pathways were significantly upregulated in CTPE cells • The molecular signature of survival signaling is prominent in CTPE cells • DEG's were validated by qRT-PCR & their expression correlates with enrichment analysis [ABSTRACT FROM AUTHOR]