Overexpression of <i>HPRT1</i> is associated with poor prognosis in head and neck squamous cell carcinoma

Ahmadi, Mohsen; Kenzerki, Maryam Eftekhari; Akrami, Seyed Mohammad; Pashangzadeh, Salar; Hajiesmaeili, Fatemeh; Rahnavard, Sahereh; Habibipour, Leila; Saffarzadeh, Negin; Mousavi, Pegah

doi:10.1002/2211-5463.13250

Cited by 19 publications

(25 citation statements)

References 55 publications

(68 reference statements)

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“…It has been reported that HPRT1 is significantly elevated in multiple cancer types ( 53 , 54 ) and is associated with a poor prognosis due to the increased demand for nucleotide synthesis during tumor cell proliferation ( 55 , 56 ). In both HNSCC and its subclass oral squamous cell carcinoma, multiple studies have demonstrated that HPRT1 was overexpressed and significantly correlated with the poor prognosis of patients ( 57 , 58 ). HPRT1 was also found to be associated with drug resistance, such as cisplatin, in cancer cells and has been proposed as a therapeutic target of chemotherapeutic drugs ( 58 , 59 ).…”

Section: Discussionmentioning

confidence: 99%

A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma

Zou

Wang

et al. 2022

Front. Immunol.

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BackgroundIn the era of immunotherapy, predictive or prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC) are urgently needed. Metabolic reprogramming in the tumor microenvironment (TME) is a non-negligible reason for the low therapeutic response to immune checkpoint inhibitor (ICI) therapy. We aimed to construct a metabolism-related gene prognostic index (MRGPI) for HNSCC bridging metabolic characteristics and antitumor immune cycling and identified the immunophenotype, genetic alternations, potential targeted inhibitors, and the benefit of immunotherapy in MRGPI-defined subgroups of HNSCC.MethodsBased on The Cancer Genome Atlas (TCGA) HNSCC dataset (n = 502), metabolism-related hub genes were identified by the weighted gene co-expression network analysis (WGCNA). Seven genes were identified to construct the MRGPI by using the Cox regression method and validated with an HNSCC dataset (n = 270) from the Gene Expression Omnibus (GEO) database. Afterward, the prognostic value, metabolic activities, genetic alternations, gene set enrichment analysis (GSEA), immunophenotype, Connectivity map (cMAP), and benefit of immunotherapy in MRGPI-defined subgroups were analyzed.ResultsThe MRGPI was constructed based on HPRT1, AGPAT4, AMY2B, ACADL, CKM, PLA2G2D, and ADA. Patients in the low-MRGPI group had better overall survival than those in the high-MRGPI group, consistent with the results in the GEO cohort (cutoff value = 1.01). Patients with a low MRGPI score display lower metabolic activities and an active antitumor immunity status and more benefit from immunotherapy. In contrast, a higher MRGPI score was correlated with higher metabolic activities, more TP53 mutation rate, lower antitumor immunity ability, an immunosuppressive TME, and less benefit from immunotherapy.ConclusionThe MRGPI is a promising indicator to distinguish the prognosis, the metabolic, molecular, and immune phenotype, and the benefit from immunotherapy in HNSCC.

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Section: Discussionmentioning

confidence: 99%

A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma

Zou

Wang

et al. 2022

Front. Immunol.

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“…It plays a crucial role in regulating the cell cycle and has been reported to be overexpressed in a variety of cancers ( 45 ). The elevated expression of the HPRT1 gene is associated with the progression of HNSCC, which may serve as a useful indicator for early detection, risk stratification, and targeted therapy in HNSCC patients ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Identify metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 as potential prognostic markers and correlate with immune infiltrates in head and neck squamous cell carcinoma

Chen

Jia

et al. 2022

Front. Immunol.

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Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of head and neck squamous cell carcinoma (HNSCC) with poor prognosis. Metabolic reprogramming may regulate the tumor microenvironment (TME) by adapting quickly to cellular stress and regulating immune response, but its role in HSCC has not been reported. We used the nCounter® Metabolic Pathways Panel to investigate metabolic reprogramming, cellular stress, and their relationship in HSCC tissues and adjacent normal tissues. Metabolism-related pathways nucleotide synthesis and glycolysis pathways were significantly upregulated, while amino acid synthesis and fatty acid oxidation pathways were significantly downregulated in HSCC tissues compared to adjacent normal tissues. There is a significant correlation between metabolism-related pathways and cellular stress pathways. Enrichment of immune cell and tumor infiltrating lymphocyte (TIL) analysis showed changes in immune responses between HSCC tissues and adjacent normal tissues. Overall survival analysis showed that upregulated genes CD276, LDHB, SLC3A2, EGFR, SLC7A5, and HPRT1 are potential unfavorable prognostic markers in HNSCC, while downregulated genes EEA1, IDO1, NCOA2, REST, CCL19, and ALDH2 are potential favorable prognostic markers in HNSCC. Moreover, metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 are correlated with immune infiltrates in HNSCC. These results suggest that metabolic reprogramming occurs and correlates with cellular stress and immune response in HSCC, which may help researchers understand mechanisms of metabolic reprogramming and develop effective immunotherapeutic strategies in HNSCC.

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“…HPRT1 is an important protein that provides the necessary components for cell growth and is highly expressed in most tissues. HPRT1 has traditionally been used as a housekeeping gene; however, many recent studies have found a potential relationship with various types of cancer [ 6 , 7 , 8 ]. HPRT1 overexpression was significantly correlated with the poor prognosis of patients with HNSCC [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…HPRT1 has traditionally been used as a housekeeping gene; however, many recent studies have found a potential relationship with various types of cancer [ 6 , 7 , 8 ]. HPRT1 overexpression was significantly correlated with the poor prognosis of patients with HNSCC [ 7 ]. HPRT1 was also found to be associated with drug resistance in cancer cells and has been proposed as a therapeutic target of chemotherapeutic drugs [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

Jiao

et al. 2022

Cancers

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Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be highly expressed in various cancer types, especially in head and neck squamous cell carcinoma (HNSCC). Therefore, we measured HPRT1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between HPRT1 expression and clinical pathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC), a common type of HNSCC. We built OSCC cells with stable knockdown and overexpression of HPRT1 to observe its influence on chemoresistance and malignancy in vitro and vivo. We found that highly expressed HPRT1 was associated with a poor prognosis and could promote resistance to cisplatin (CDDP) in OSCC cells in both in vitro and in vivo. An RNA sequence assay was carried out to explore the mechanism of function of HPRT1, we found that HPRT1 could positively regulate the expression of MMP1 and the activation of the PI3K/AKT pathway, to regulate the resistance to CDDP of OSCC. In conclusion, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 overexpression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis. HPRT1 may be a potential prognostic biomarker and therapeutic target in OSCC.

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Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 19 publications

References 55 publications

A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma

A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma

Identify metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 as potential prognostic markers and correlate with immune infiltrates in head and neck squamous cell carcinoma

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

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