Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer
Open Access
- 25 June 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Background: Hypoxia 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. Methods: We 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. Results: We 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. Conclusions: The 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.Keywords
This publication has 62 references indexed in Scilit:
- TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progressionTrends in Immunology, 2010
- Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasionBritish Journal of Cancer, 2009
- How To Build and Interpret a Nomogram for Cancer PrognosisJournal of Clinical Oncology, 2008
- Hypoxia and cancerJournal of Molecular Medicine, 2007
- Decision Curve Analysis: A Novel Method for Evaluating Prediction ModelsMedical Decision Making, 2006
- Phosphorylation and activation of STAT proteins by hypoxia in breast cancer cellsThe Breast, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Hypoxia-inducible Factor-1α is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal TumorJapanese Journal of Clinical Oncology, 2005
- The Hallmarks of CancerCell, 2000
- Modulation of tumor oxygenationInternational Journal of Radiation Oncology*Biology*Physics, 1998