A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients.

Zhang, Baohui; Tang, Bufu; Gao, Jianyao; Li, Jiatong; Kong, Lingming; Qin, Ling

doi:10.21203/rs.3.rs-17783/v3

Cited by 3 publications

(1 citation statement)

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“…The immunological components of the TME can inhibit or promote tumor development (22). Recently, the significance of hypoxia in promoting tumor immunosuppression and immune escape has received increasing attentions (23,24). It is important to understand the potential mechanisms that are involved between hypoxia and the tumor immune microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer

et al. 2021

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BackgroundHypoxia is one driving factor of gastric cancer. It causes a series of immunosuppressive processes and malignant cell responses, leading to a poor prognosis. It is clinically important to identify the molecular markers related to hypoxia.MethodsWe screened the prognostic markers related to hypoxia in The Cancer Genome Atlas database, and a risk score model was developed based on these markers. The relationships between the risk score and tumor immune microenvironment were investigated. An independent validation cohort from Gene Expression Omnibus was applied to validate the results. A nomogram of risk score model and clinicopathological factor was developed to individually predict the prognosis.ResultsWe developed a hypoxia risk score model based on SERPINE1 and EFNA3. Quantified real-time PCR was further applied to verified gene expressions of SERPINE1 and EFNA3 in gastric cancer patients and cell lines. A high-risk score is associated with a poor prognosis through the immunosuppressive microenvironment and immune escape mechanisms, including infiltration of immunosuppressive cells, expression of immune checkpoint molecules, and enrichment of signal pathways related to cancer and immunosuppression. The nomogram basing on the hypoxia-related risk score model showed a good ability to predict prognosis and high clinical net benefits.ConclusionsThe hypoxia risk score model revealed a close relationship between hypoxia and tumor immune microenvironment. The current study potentially provides new insights of how hypoxia affects the prognosis, and may provide a new therapeutic target for patients with gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer

et al. 2021

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Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

Liu

Rong

et al. 2021

Front. Immunol.

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Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

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Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer

Tan

Cheng

Wen

et al. 2021

MBE

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<abstract> <sec><title>Background</title>Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. </sec> <sec><title>Methods</title>The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. </sec> <sec><title>Results</title>We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. </sec> <sec><title>Conclusions</title>Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy. </sec> </abstract>

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A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients.

Cited by 3 publications

References 28 publications

Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer

Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer

Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer

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