Abstract
BackgroundImmunotherapy has evolved as a critical option to treat diverse cancers. The active response to immunotherapy relies on the unique interaction between cancer and the tumor microenvironment (TME). Angiogenesis is one of the hallmarks of cancer. However, the association between angiogenesis and clinical outcome, immune cell infiltration, and immunotherapy remains unknown in gastric cancer (GC).MethodsWe systematically assessed 36 angiogenesis-associated genes (AAGs) and comprehensively identified the correlation between angiogenesis and transcriptional patterns, prognosis, and immune cell infiltration. The AAG_score was applied to quantify the angiogenesis subtypes of each patient. We then evaluated their values in prognostic prediction and therapeutic responses in GC.ResultsWe discussed the mutations of AAGs in GC specimens from genetic levels and identified their expression patterns from TCGA and GEO cohorts. We determined two different molecular subtypes and observed that AAG mutations were related to patients’ clinicopathological characteristics, prognosis, and infiltrating TME. Next, an AAG_score for predicting overall survival (OS) was established and its reliable predictive ability in GC patients was confirmed. Furthermore, we created a highly reliable nomogram to facilitate the clinical viability of the AAG_score. A low AAG_score, characterized by elevated microsatellite instability-high, mutation burden, and immune activation, demonstrated a superior OS. Additionally, the AAG_score was remarkedly correlated with the cancer stem cell index and drug susceptibility.ConclusionCollectively, we identified a prognostic AAG signature for GC patients. This signature may contribute to clarifying the characteristics of TME and enable the exploration of more potent immunotherapy strategies.
Highlights
Immunotherapy is a blooming treatment modality for diverse tumors, and its effectiveness against tumors is being confirmed by a growing body of clinical studies [1–3]
A protein-protein interaction (PPI) analysis through the string website was established to reveal the interactivity of DEGs, which indicated that VEGFA, SPP1, POSTN, VTN, COL3A1, and TIMP1 were hub genes (Figure 1B)
We explore CNV mutational incidence, which indicated that 36 associated genes (AAGs) demonstrated evident CNV alterations (Figure 1D)
Summary
Immunotherapy is a blooming treatment modality for diverse tumors, and its effectiveness against tumors is being confirmed by a growing body of clinical studies [1–3]. The studies of ICIs for PD-1, PD-L1, and CTLA-4 are emerging and clinical reports have proven their safety and effectiveness [4, 5]. The TME consists of various factors, including tumor cells, blood vessels, infiltrating immune cells, stromal cells, tissue fluid, and cytokines [7]. Tumor cells promote angiogenesis and inflammation, evading the surveillance and clearance of the immune system [8]. The active response to immunotherapy relies on the unique interaction between cancer and the tumor microenvironment (TME). Angiogenesis is one of the hallmarks of cancer. The association between angiogenesis and clinical outcome, immune cell infiltration, and immunotherapy remains unknown in gastric cancer (GC)
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