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pmid:35127477

A Robust Metabolic Enzyme-Based Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Zizhao Mai · Huan Chen · Mingshu Huang · Xinyuan Zhao · Li Cui

Frontiers in oncology · 2021 doi:10.3389/fonc.2021.770241

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A Robust Metabolic Enzyme-Based Prognostic Signature for Head and Neck Squamous Cell Carcinoma.
doi
10.3389/fonc.2021.770241
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Zizhao Mai
[1]
Huan Chen
[2]
Mingshu Huang
[3]
Xinyuan Zhao
[4]
Li Cui
journal
Frontiers in oncology
year
2021
abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known. METHODS: Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated. RESULTS: A total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells. CONCLUSION: Our study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. Moreover, the nomogram model might provide useful guidance for the precision treatment of HNSCC.
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However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known.\nMETHODS: Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated.\nRESULTS: A total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells.\nCONCLUSION: Our study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. 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In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of", "Materials and Methods Cell Culture and Transfection Both SCC1 and SCC23 were cultured in Dulbecc", "r in a humidified atmosphere. The cells were transfected with siTXNRD1 and siCTRL using Lipofectamine", "RD1 and siCTRL using Lipofectamine® RNA iMAX Transfection Reagent (Invitrogen, Carlsbad, CA, USA). Sta"], "order_basis": "paper_text_order:1469", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["re and Transfection Both SCC1 and SCC23 were cultured in Dulbecco’s modified Eagle’s medium (DMEM) (G"], "order_basis": "paper_text_order:1829", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The multivariate Cox regression analysis revealed that only risk score (p<0.001, HR=2.047) was the independent prognostic factor for HNSCC ( Figure 7B )."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}