A prognostic model for STAD based on hypoxia- and immune-related genes

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Introduction: Characterized by vast heterogeneity, gastric cancer (GC) is one of the leading causes of cancer-related deaths. A specific prognostic model is necessary for the improvement of clinical treatment strategies. Hypoxia is a common feature in the tumor microenvironment that promotes tumor progression. However, the current evaluation of the hypoxic tumor immune microenvironment in GC is still inadequate. Material and methods: With sequence data and single nucleotide variants data obtained from The Cancer Genome Atlas-STAD dataset as well as hypoxia- and immune-related genes acquired from MsigDB and ImmPort, a hypoxia-immune-based gene signature of stomach adenocarcinoma (STAD) was built by Cox regression analysis. The risk score could be used as an independent prognostic factor. Results: The receiver operating characteristic curve and survival curve showed the accuracy of the model. Pearson correlation analysis showed that DUSP1, one of the hypoxia- and immune-related feature genes, was positively correlated with immune cell scores and immune-related function scores. In addition, low-risk group peers were found to be in higher immune infiltration status and had a higher immunophenoscore as demonstrated by single-sample Gene Set Enrichment Analysis (GSEA), indicating a better response to immune checkpoint inhibitor (ICI) treatment among the low-risk group. q-PCR results showed that DUSP1, IGFBP1, CGB5, GPC3 and EGF were significantly highly expressed in STAD cells, while FAM3D and FGF8 were significantly down-regulated. Conclusions: Overall, our study not only paves the way for future studies focusing on hypoxia and the immune microenvironment but also improves STAD patients' prognosis and their response to immunotherapy.

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