Uncovering the Heterogeneity of Signaling Pathways in Skin Cutaneous Melanoma: Insights into Prognostic Values and Immune Interactions

Background: Signaling pathways play crucial roles in tumor cells. However, functional heterogeneity of signaling pathways in skin cutaneous melanoma (SKCM) has not been established.

Methods: Based on a recent computational pipeline, pathway activities between SKCM and normal samples were identified.

Results: The results showed that high activities in 12 pathways were associated with poor prognoses, while high activities in 17 pathways were associated with favorable prognoses. Interestingly, elevated metabolic pathway activity was unfavorable, whereas elevated immune activity was favorable for SKCM. Unfavorably elevated metabolic pathways strongly correlated with Wnt/beta-catenin signaling. Conversely, favorable pathways, such as glycosaminoglycan biosynthesis and keratan sulfate, were strongly correlated with anti-tumor pathways. Moreover, the activities of favorable pathways were strongly positively correlated with infiltrating CD8⁺ T cells, macrophages M1, immune score, and stromal score, all of which were favorable for SKCM.

Conclusion: Taken together, our study provides insights into the characteristics of several pathways in SKCM.