This divergence is best explained by the dual role of the CREM gene, as it can act as an enhancer or repressor of transcription, depending on which isoform is expressed.3 Indeed, isoform-specific expression of CREM has already been linked to prostate cancer; the ICER isoform has been identified as a possible tumor suppressor22 and CREM a possible coregulator of apoptosis and carcinogenesis with several differentially expressed miRNAs, affecting prostate cancer progression.7 A study in another cancer type, esophageal squamous cell carcinoma (ESCC), found CREM to have prognostic value. This evidence concerns the gene CREM and esophageal squamous cell carcinoma.