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...

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Main Authors: Zicheng Wang, Xisong Liang, Hao Zhang, Zeyu Wang, Xun Zhang, Ziyu Dai, Zaoqu Liu, Jian Zhang, Peng Luo, Jiarong Li, Quan Cheng
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/5209607
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author Zicheng Wang
Xisong Liang
Hao Zhang
Zeyu Wang
Xun Zhang
Ziyu Dai
Zaoqu Liu
Jian Zhang
Peng Luo
Jiarong Li
Quan Cheng
author_facet Zicheng Wang
Xisong Liang
Hao Zhang
Zeyu Wang
Xun Zhang
Ziyu Dai
Zaoqu Liu
Jian Zhang
Peng Luo
Jiarong Li
Quan Cheng
author_sort Zicheng Wang
collection DOAJ
description 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.
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spelling doaj-art-3fc27ac4caeb4aecbb55a2fa710cf3d92025-08-20T02:08:04ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/5209607Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric CancerZicheng Wang0Xisong Liang1Hao Zhang2Zeyu Wang3Xun Zhang4Ziyu Dai5Zaoqu Liu6Jian Zhang7Peng Luo8Jiarong Li9Quan Cheng10Hepatobiliary SurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of Interventional RadiologyDepartment of OncologyDepartment of OncologyDepartment of General SurgeryDepartment of NeurosurgeryHypoxia 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.http://dx.doi.org/10.1155/2022/5209607
spellingShingle Zicheng Wang
Xisong Liang
Hao Zhang
Zeyu Wang
Xun Zhang
Ziyu Dai
Zaoqu Liu
Jian Zhang
Peng Luo
Jiarong Li
Quan Cheng
Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
Journal of Immunology Research
title Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
title_full Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
title_fullStr Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
title_full_unstemmed Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
title_short Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer
title_sort identification of a hypoxia angiogenesis lncrna signature participating in immunosuppression in gastric cancer
url http://dx.doi.org/10.1155/2022/5209607
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