Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Chu, Manru; Zheng, Ke; Li, Xiaojie; Luo, Zhiqiang; Yang, Xin; Wei, Changbo

doi:10.1155/2022/2371057

Cited by 5 publications

(6 citation statements)

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“…54 SLC2A3 exerts multiple biological functions in different cancers, including tumor EMT, ferroptosis, glycolytic reprogramming, drug resistance and immunity. [55][56][57][58][59] Immune cell infiltration analysis showed that SLC11A1 and SLC2A3 expression was positively correlated with the infiltration levels of neutrophils, macrophages, dendritic cells, CD4+ T cells and CD8+ T cells. Moreover, the higher the expression levels of SLC11A1 and SLC2A3, the lower the tumor purity.…”

Section: Discussionmentioning

confidence: 99%

“…Reportedly, SLC11A1 not only predicts the prognosis of colorectal cancer and hepatocellular carcinoma 52,53 but also serves as a stratification indicator for immunotherapy or chemotherapy in glioma patients 54 . SLC2A3 exerts multiple biological functions in different cancers, including tumor EMT, ferroptosis, glycolytic reprogramming, drug resistance and immunity 55–59 . Immune cell infiltration analysis showed that SLC11A1 and SLC2A3 expression was positively correlated with the infiltration levels of neutrophils, macrophages, dendritic cells, CD4+ T cells and CD8+ T cells.…”

Section: Discussionmentioning

confidence: 99%

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Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Wang,

Qiu

et al. 2024

The Journal of Gene Medicine

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BackgroundColon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients.MethodsWe first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression‐free survival (PFS) were assessed by Kaplan–Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues.ResultsWe established and validated a risk scoring model based on neutrophil‐related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high‐risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy.ConclusionsThe low‐risk group showed better OS and PFS than the high‐risk group in the neutrophil‐related gene‐based risk model. Patients in the high‐risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Wang,

Qiu

et al. 2024

The Journal of Gene Medicine

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“…Consistently reported in the literature, SLC2A3 shows overexpression in the basal and suprabasal layer cells of OSCC, demonstrating increased glucose uptake [ 16 ]. Also, bioinformatics analyses by Chu predict that upregulated SLC2A3 may link to advanced clinical stages and lymph node metastasis [ 17 ]. Fernanda’s IHC analysis confirms high SLC2A3 expression is associated with advanced tumor stages, vascular invasion, and decreased disease-free survival [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma

Jiang,

Xu,

2024

PLoS ONE

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Backgrounds Oral squamous cell carcinoma is a malignant tumor of the head and neck, and its molecular mechanism remains to be explored. Methods By analyzing the OSCC data from the TCGA database, we found that SLC2A3 is highly expressed in OSCC patients. The expression level of SLC2A3 was verified by RT-PCR and western blotting in OSCC cell lines. The function of SLC2A3 in OSCC cell lines and Lactic acid in SLC2A3-knockdown OSCC cells were detected by colony formation, CCK8, transwell, and wound healing assays. The effect of SLC2A3 on tumor growth and metastasis was tested in vivo. GSEA and Western blot were used to analyze and validate tumor phenotypes and signaling pathway molecules. Results We analyzed OSCC datasets in the TCGA database and found that SLC2A3 had abnormally high expression and was associated with poor prognosis. We also found that oral squamous cell carcinoma cells had increased proliferation, migration, invasion, EMT phenotype, and glycolysis due to SLC2A3 overexpression. Conversely, SLC2A3 knockdown had the opposite effect. Our in vivo experiments confirmed that SLC2A3 overexpression promoted tumor growth and metastasis while knockdown inhibited it. We also observed that high SLC2A3 expression led to EMT and the activation of the TGF-β signaling pathway, while knockdown inhibited it. Interestingly, exogenous lactic acid restored the EMT, proliferation, migration, and invasion abilities of oral cancer cells inhibited by knocking down SLC2A3. Conclusions Our study reveals that SLC2A3 expression was up-regulated in OSCC. SLC2A3 activates the TGF-β signaling pathway through lactic acid generated from glycolysis, thus regulating the biological behavior of OSCC.

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“…The oncogenic potential of SLC2A3 has been extensively investigated. An overexpression or copy number gain of SLC2A3 has been witnessed in liquid and solid tumors [ 103 , 104 , 105 , 106 , 107 , 108 ]. For instance, high levels of SLC2A3 were associated with unfavorable outcomes in CRC, gastric (GC), and head and neck squamous cell carcinoma (HNSCC) [ 105 , 106 , 107 ].…”

Section: Discussionmentioning

confidence: 99%

“…An overexpression or copy number gain of SLC2A3 has been witnessed in liquid and solid tumors [ 103 , 104 , 105 , 106 , 107 , 108 ]. For instance, high levels of SLC2A3 were associated with unfavorable outcomes in CRC, gastric (GC), and head and neck squamous cell carcinoma (HNSCC) [ 105 , 106 , 107 ]. Additionally, SLC2A3 seems directly targeted by miRNAs along tumorigenesis [ 109 , 110 , 111 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

Palma

Carbonnier

Salvatore

et al. 2022

Cancers

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(1) Background: Long non-coding RNAs may constitute epigenetic biomarkers for the diagnosis, prognosis, and therapeutic response of a variety of tumors. In this context, we aimed at assessing the diagnostic and prognostic value of the recently described long intergenic non-coding RNA 01087 (LINC01087) in human cancers. (2) Methods: We studied the expression of LINC01087 across 30 oncological indications by interrogating public resources. Data extracted from the TCGA and GTEx databases were exploited to plot receiver operating characteristic curves (ROC) and determine the diagnostic performance of LINC01087. Survival data from TCGA and KM-Plotter directories allowed us to graph Kaplan–Meier curves and evaluate the prognostic value of LINC01087. To investigate the function of LINC01087, gene ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed. Furthermore, interactions between LINC01087 and both miRNA and mRNA were studied by means of bioinformatics tools. (3) Results: LINC01087 was significantly deregulated in 7 out of 30 cancers, showing a predominant upregulation. Notably, it was overexpressed in breast (BC), esophageal (ESCA), and ovarian (OV) cancers, as well as lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD), and uterine carcinosarcoma (UCS). By contrast, LINC01087 displayed downregulation in testicular germ cell tumors (TGCT). ROC curve analyses identified LINC01087 as a potential diagnostic indicator in BC, ESCA, OV, STAD, and TGCT. Moreover, high and low expression of LINC01087 predicted a favorable prognosis in BC and papillary cell carcinoma, respectively. In silico analyses indicated that deregulation of LINC01087 in cancer was associated with a modulation of genes related to ion channel, transporter, and peptide receptor activity. (4) Conclusions: the quantification of an altered abundance of LINC01087 in tissue specimens might be clinically useful for the diagnosis and prognosis of some hormone-related tumors, including BC, OV, and TGCT, as well as other cancer types such as ESCA and STAD. Moreover, our study revealed the potential of LINC01087 (and perhaps other lncRNAs) to regulate neuroactive molecules in cancer.

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Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Cited by 5 publications

References 51 publications

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

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