Identification and validation of a hypoxia-related prognostic and immune microenvironment signature in bladder cancer

Sun, Xianchao; Zhou, Zhen; Zhang, Ying; Wang, Jinyou; Zhao, Xiaofeng; Jin, Liang; Zhai, Ting‐Shuai; Liu, Xiang; Zhang, Jiaxin; Mei, Wangli; Zhang, Bihui; Luo, Ming; Yao, Xudong; Ye, Lin

doi:10.1186/s12935-021-01954-4

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…In this study, according to GO and KEGG analyses, we first verified that the prognostic model has a significant correlation with most ARGs. Studies have proved that hypoxia can promote cell proliferation in tumors and the progression of tumor conversion to the malignant phenotype ( Sun et al, 2021 ). Meanwhile, hypoxia can also protect macrophages from ferroptosis ( Fuhrmann et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

Yan

Liu

et al. 2022

Front. Genet.

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Background: Although ferroptosis has been validated to play a crucial role in some types of tumors, the influence of ferroptosis-related genes (FRGs) on the immune microenvironment in low-grade glioma (LGG) remains unclear. In this research, we screen the FRGs to assess the prognosis value and immune microenvironment in LGG, to provide reliable diagnosis and treatment evidence for the clinic.Methods: A total of 1,239 patients of LGG samples were selected for subsequent analyses from The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and the Repository of Molecular Brain Neoplasia Data datasets. Univariate Cox regression analysis was used to screen for prognostic FRGs. Consensus clustering was utilized to determine ferroptosis subtypes of LGG patients. Next, the prognostic model was constructed based on differentially expressed FRGs and validation in the validating datasets. The immune microenvironment, biological pathway, and hypoxia score were explored by single-sample gene set enrichment analysis. The potential response of chemotherapy and immune checkpoint blockade therapy was also estimated. In addition, the correlation between the risk score and autophagy-related genes was examined by the Pearson correlation coefficient.Results: A total of three ferroptosis subtypes were identified by consensus clustering for prognostic FRGs which exhibited different outcomes, clinicopathological characteristics, and immune microenvironment. Afterward, a prognostic model that performed great predictive ability based on nine prognostic FRGs has been constructed and validated. Moreover, the prognostic model had the potential to screen the sensitivity to chemotherapy and immunotherapy in LGG patients. Finally, we also found that the prognostic model has a great connection to autophagy and hypoxia.Conclusion: We developed a ferroptosis-related prognostic model which strongly linked to diagnosis, treatment, prognosis, and recurrence of LGG. This study also reveals the connection between ferroptosis and tumor immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

Yan

Liu

et al. 2022

Front. Genet.

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“…Immune checkpoint inhibitors are a potential treatment for cancer therapy that block key molecules and have shown impressive efficacy against cancer, especially revolutionizing the management of metastatic and locally advanced BCa ( de Kouchkovsky et al, 2021 ; Sun et al, 2021b ). In the multifaceted immune regulation of BCa, CTLA4 is one of the primary immune checkpoints.…”

Section: Discussionmentioning

confidence: 99%

A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer

Chen

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Hypoxia is a common feature in various tumors that regulates aggressiveness. Previous studies have demonstrated that some dysregulated long non-coding RNAs (lncRNAs) are correlated with tumor progression, including bladder cancer (BCa). However, the prognostic effect of hypoxia-related lncRNAs (HRLs) and their clinical relevance, as well as their regulatory effect on the tumor immune microenvironment, are largely unknown in BCa. A co-expression analysis between hypoxia genes and lncRNA expression, which was downloaded from the TCGA database, was performed to identify HRLs. Univariate Cox regression analysis was performed to select the most desirable lncRNAs for molecular subtype, and further LASSO analysis was performed to develop a prognostic model. This molecular subtype based on four HRLs (AC104653, AL136084, AL139393, and LINC00892) showed good performance in the tumor microenvironment and tumor mutation burden. The prognostic risk model suggested better performance in predicting BCa patients’ prognosis and obtained a close correlation with clinicopathologic features. Furthermore, four of five first-line clinical chemotherapies showed different sensitivities to this model, and nine immune checkpoints showed different expression in the molecular subtypes or the risk model. In conclusion, this study indicates that this molecular subtype and risk model based on HRLs may be useful in improving the prognostic prediction of BCa patients with different clinical situations and may help to find a useful target for tumor therapy.

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“…As evident from the table, every signature consists of its own set of genes, even if it was derived from the same tumor type, with minimal overlap with other signatures. The conclusions of most papers underscore the immunosuppressive power of hypoxia in bladder cancer (189,213), breast cancer (214), colorectal cancer (CRC) (191,216,217), head and neck squamous cell carcinoma (218), hepatocellular carcinoma (HCC) (221)(222)(223), lung cancer (195,225,226), melanoma (196), oral squamous cell carcinoma (227), osteosarcoma (229), ovarian carcinoma (230) and pancreatic ductal adenocarcinoma (PDAC) (197,231). In the case of bladder cancer, two other studies determined the presence of high infiltration of immune cells in the high-risk group and found positive correlations between immune score and the risk score (190,212).…”

Section: Unraveling the Hypoxia-immune Contexture In Silico: The Hits...mentioning

confidence: 99%

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

et al. 2022

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Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response. The tumor cell-immune cell crosstalk in the context of a hypoxic TME tips the balance towards a cold and immunosuppressed microenvironment that is resistant to immune checkpoint inhibitors (ICI). Nonetheless, evidence is emerging that could make hypoxia an asset for improving response to ICI. Tackling the tumor immune contexture has taken on an in silico, digitalized approach with an increasing number of studies applying bioinformatics to deconvolute the cellular and non-cellular elements of the TME. Such approaches have additionally been combined with signature-based proxies of hypoxia to further dissect the turbulent hypoxia-immune relationship. In this review we will be highlighting the mechanisms by which hypoxia impacts immune cell functions and how that could translate to predicting response to immunotherapy in an era of machine learning and computational biology.

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Identification and validation of a hypoxia-related prognostic and immune microenvironment signature in bladder cancer

Cited by 15 publications

References 31 publications

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

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