Open Access

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer

  • Authors:
    • Weijian Zhang
    • Dishu Zhou
    • Shuya Song
    • Xinxin Hong
    • Yifei Xu
    • Yuqi Wu
    • Shiting Li
    • Sihui Zeng
    • Yanzi Huang
    • Xinbo Chen
    • Yizhong Liang
    • Shaoju Guo
    • Huafeng Pan
    • Haiwen Li
  • View Affiliations

  • Published online on: December 21, 2023     https://doi.org/10.3892/ol.2023.14203
  • Article Number: 70
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) is the fifth most common cause of cancer‑associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA‑seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription‑quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2‑related differentially expressed genes were enriched predominantly in ‘chylomicron assembly’, ‘plasma lipoprotein particle assembly’, ‘high‑density lipoprotein particle’, ‘chylomicron’, ‘triglyceride‑rich plasma lipoprotein particle’, ‘very‑low‑density lipoprotein particle’. ‘intermembrane lipid transfer activity’, ‘lipoprotein particle receptor binding’, ‘cholesterol transporter activity’ and ‘intermembrane cholesterol transfer activity’. In addition, ‘cholesterol metabolism’, and ‘fat digestion and absorption’ were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease‑specific survival and progression‑free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.
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February-2024
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Spandidos Publications style
Zhang W, Zhou D, Song S, Hong X, Xu Y, Wu Y, Li S, Zeng S, Huang Y, Chen X, Chen X, et al: Prediction and verification of the prognostic biomarker <em>SLC2A2</em> and its association with immune infiltration in gastric cancer. Oncol Lett 27: 70, 2024
APA
Zhang, W., Zhou, D., Song, S., Hong, X., Xu, Y., Wu, Y. ... Li, H. (2024). Prediction and verification of the prognostic biomarker <em>SLC2A2</em> and its association with immune infiltration in gastric cancer. Oncology Letters, 27, 70. https://doi.org/10.3892/ol.2023.14203
MLA
Zhang, W., Zhou, D., Song, S., Hong, X., Xu, Y., Wu, Y., Li, S., Zeng, S., Huang, Y., Chen, X., Liang, Y., Guo, S., Pan, H., Li, H."Prediction and verification of the prognostic biomarker <em>SLC2A2</em> and its association with immune infiltration in gastric cancer". Oncology Letters 27.2 (2024): 70.
Chicago
Zhang, W., Zhou, D., Song, S., Hong, X., Xu, Y., Wu, Y., Li, S., Zeng, S., Huang, Y., Chen, X., Liang, Y., Guo, S., Pan, H., Li, H."Prediction and verification of the prognostic biomarker <em>SLC2A2</em> and its association with immune infiltration in gastric cancer". Oncology Letters 27, no. 2 (2024): 70. https://doi.org/10.3892/ol.2023.14203