Table 1_Delineation of molecular subtypes based on pathway activation signatures reveals intrinsic tumor heterogeneity and pan-cancer shared features.xlsx

C4 showed elevated activity of oncogenic signaling, cellular processes-related, and DDR pathways. Notably, compared with C2 and C4, C1 and C3 displayed enhanced immune score, increased CD8+T cell infiltration and higher expression of genes involving in antigen processing and presentation, immunogenic cell death and immune checkpoint. C3 demonstrated the most favorable overall survival and the lowest proportion of progressive/stable disease patients, followed by C1, whereas C2 and C4 were associated with inferior clinical outcomes.

C3 was susceptible to multiple agents, while C1 showed multidrug resistance. Moreover, in vitro cellular experiments demonstrated that combined treatment with inhibitors targeting activated pathways yielded superior inhibitory effects relative to monotherapy for C1, C2 and C4.</p>Conclusions<p>Overall, our study defined four molecular subtypes based on the pathway activation profiles, with each subtype displaying unique features in pathway activation, clinical manifestations, treatment response, survival prognosis, immune microenvironment, and drug sensitivity.

These findings may provide potential valuable insights for the precise diagnosis and treatment of cancer.</p>