Abstract
BACKGROUND: Skin cutaneous melanoma (SKCM) is a highly aggressive disease with a poor prognosis for advanced tumors. Anoikis is a caspase-dependent cell death process triggered by extracellular matrix (ECM) detachment, rectifies detachment-induced metabolic defects that compromise cell survival, recent study revealed the crucial role of anoikis for cancer cells to survive during metastasis. However, limited research focused on the role of anoikis in SKCM. METHODS: Our study utilized the 27 anoikis-related genes (ARGs) to divide SKCM patients into two clusters, and obtain differentially expressed genes (DEGs) for each cluster. These DEGs were used in stepwise Cox regression analysis to develop a prediction model for SKCM patients consisting of nine ARGs, called the anoikis-related signature (ARS). Subsequently, we used the risk scores calculated from the ARS to divide SKCM patients into two groups and explored differences in immune microenvironment, immune checkpoint reactivity, and drug sensitivity between the groups. RESULTS: Nine ARGs were identified to stratify SKCM patients into two risk groups, patients in the high-risk group had a poor prognosis and suppressed immune cell infiltration. Moreover, higher expression of immune checkpoint molecules and a greater sensitivity to immunotherapy and chemotherapy drugs were observed in the low-risk group. Finally, all of the ARS hub genes were found to be upregulated in SKCM tissues and cell lines. CONCLUSION: A novel ARGs signature was identified for predicting the prognosis of SKCM. Based on the immune landscape associated with ARS discovered in our study, targeting ARS hub genes may be a promising treatment for SKCM.