Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer

Hypoxia and angiogenesis are the leading causes of tumor progression, and their strong correlation has been discovered in many cancers. However, their collective function's prognostic and biological roles were not reported in gastric cancer. Hence, we aimed to investigate the effects of hypoxia and angiogenesis on gastric cancer via sequencing data. This study used weighted gene coexpression network analysis and random forest regression to build a hypoxia-angiogenesis-related model (HARM) via the TCGA-STAD lncRNA data. It estimated the HARM's correlation with clinical features and its accuracy for survival prediction. Sequential functional analyses were conducted to investigate its biological role, and we next sought the immune landscape status and immunological function variation by ESTIMATE score calculation and GSVA, respectively. Seven different algorithms were conducted to assess the immunocyte infiltration, and TIDE score and immune checkpoint levels were compared between the high- and low-HARM groups. As a result, we found that HARM predicted patient survival with high accuracy and was correlated with higher stages of gastric cancer. Various cancer-associated pathways and macrophage-related regulations were upregulated in the high-HRAM group. The high-HARM group harbored higher immune levels, and M2 macrophages and cancer-associated fibroblasts were particularly highly unfiltered. Furthermore, globally upregulated immune checkpoints and higher TIDE scores were observed in the high-HARM group. Finally, we filtered eight drugs with lower IC50 in the high-HARM group as potential drugs for the HARM-targeted therapy. We believe this study opens up novel perspectives into the interaction between hypoxia-angiogenesis and immunosuppression and will provide novel insights for gastric cancer immunotherapy.

Automated summary

This study aimed to investigate the effects of hypoxia and angiogenesis on gastric cancer and establish a related model. The results showed that the model could accurately predict patient survival and was associated with the staging of gastric cancer. Various cancer-associated pathways and macrophage-related regulations were upregulated in the high-HARM group. The high-HARM group also exhibited higher immune levels and increased infiltration of M2 macrophages and cancer-associated fibroblasts. Additionally, globally upregulated immune checkpoints and higher TIDE scores were observed in the high-HARM group. Eight drugs with lower IC50 in the high-HARM group were identified as potential drugs for HARM-targeted therapy.