STAT6 Expression Correlates with Melanin Pigmentation in Melanomas

Background: The melanin pigment may play a significant role in influencing melanoma invasion, metastatic potential, and tumor response to therapy. Melanogenesis, the biological process responsible for melanin production, can be suppressed through activation of the Janus kinase-signal transducer and activator of transcription 6 (JAK-STAT6) signaling pathway, which results in a reduction of melanin levels. Given this mechanism, we aimed to investigate the possible association between STAT6 expression and the degree of melanin pigmentation in patients diagnosed with primary cutaneous melanomas. Methods: Analysis of mRNA expression data was conducted in a cohort of 329 melanoma tumors from The Cancer Genome Atlas (TCGA) dataset, and the relationship between STAT6 transcriptional levels and pigmentation levels was assessed. STAT6 protein content was evaluated by immunohistochemistry (IHC) in 91 tumor samples, and the results were correlated with pigmentation levels observed histologically. Results: Pigmentation scores varied significantly among groups with different STAT6 expression levels for both mRNA and protein expression (mRNA, pigment scores 1 and 2, both p < 0.05 versus pigment score 0; pigment score 3, p < 0.0001 versus pigment score 0; protein, pigmented versus non-pigmented tumors, p = 0.039). Conclusion: These findings suggest a potential association between gene and protein expression of STAT6 and melanin pigmentation levels in primary melanomas, suggesting a possible role for STAT6 in pigmentation regulation.