Objective: Anorectal mucosal melanoma is a rare and aggressive cancer with limited treatment options. Investigating specific molecular pathways may provide insight into the development and progression of this cancer. This study aims to investigate the role of chitinase-3-like protein-1 (YKL-40) in promoting the development of anorectal mucosal melanoma through the PI3K-AKT signaling pathway.
Methods: Perianal cells from healthy volunteers and melanoma cells from patients with early, middle and advanced anorectal melanoma were obtained. Western blotting was performed to detect the protein expression of PI3K, AKT, and the downstream proteins mTOR, p-mTOR, ERK, and p-ERK, respectively. Subsequently, we constructed knockout and overexpression of YKL-40 melanoma cell lines, then used western blot assay to test for YKL-40, PI3K and AKT protein expression.
Results: A significant increase in the expression of PI3K, AKT, and the downstream proteins mTOR, pmTOR, ERK, and pERK was observed in melanoma cells, and the expression of these proteins increased with the development of melanoma. After YKL-40 was knocked out, PI3K and AKT expression decreased in melanoma cells in patients with advanced melanoma. On the contrary, PI3K and AKT protein expression increased significantly after YKL-40 overexpression.
Conclusion: There is a positive correlation between the expression levels of PI3K, AKT, mTOR, p-mTOR, ERK, and p-ERK and the stage of tumor development. The PI3K-AKT signaling pathway promotes the progress of anorectal mucosal melanoma. Chitinase-3-like protein-1 (YKL-40) regulates the progression of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Investigating specific molecular pathways may provide a better understanding of anorectal mucosal melanoma. The findings from this study could contribute to the development of new diagnosis and treatment strategies for this rare and aggressive cancer. Future research directions may include investigating other possible pathways involved in melanoma progression.