Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma

Body fluids of patients with head and neck squamous cell carcinoma (HNSCC) are enriched in exosomes that reflect properties of the tumor. The aim of this study was to determine whether purine metabolites are carried by exosomes and evaluate their role as potential contributors to tumor immune escape. The gene expression levels of the purine synthesis pathway were studied using the Cancer Genome Atlas (TCGA) Head and Neck Cancer database. Exosomes were isolated from supernatants of UMSCC47 cells and from the plasma of HNSCC patients (n = 26) or normal donors (NDs; n = 5) using size exclusion chromatography. Ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to assess levels of 19 purine metabolites carried by exosomes. In HNSCC tissues, expression levels of genes involved in the purinergic pathway were upregulated indicating an accelerated purine metabolism compared to normal tissues. Exosomes from supernatants of UMSCC47 cells contained several purine metabolites, predominantly adenosine and inosine. Purine metabolite levels were enriched in exosomes isolated from the plasma of HNSCC patients compared to those isolated from NDs and carried elevated levels of adenosine (p = 0.0223). Exosomes of patients with early-stage disease and no lymph node metastasis contained significantly elevated levels of adenosine and 5′-GMP (p = 0.0247 and p = 0.0229, respectively). The purine metabolite levels in exosomes decreased in patients with advanced cancer and nodal involvement. This report provides the first evidence that HNSCC cells shuttle purine metabolites in exosomes, with immunosuppressive adenosine being the most prominent purine. Changes in the content and levels of purine metabolites in circulating exosomes reflect disease progression in HNSCC patients.

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Ferroptosis Driver SOCS1 and Suppressor FTH1 Independently Correlate With M1 and M2 Macrophage Infiltration in Head and Neck Squamous Cell Carcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.727762 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhang-Wei Hu ◽

Yi-Hui Wen ◽

Ren-Qiang Ma ◽

Lin Chen ◽

Xue-Lan Zeng ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Macrophage Infiltration ◽

M2 Macrophage ◽

Expression Levels

ObjectiveTo investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.Materials and MethodsA list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.ResultsAnalysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.ConclusionsThe ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

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Diagnostic and Prognostic Value of MicroRNAs in Metastasis and Recurrence of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.711171 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ke Qiu ◽

Yao Song ◽

Yufang Rao ◽

Qiurui Liu ◽

Danni Cheng ◽

...

Keyword(s):

Systematic Review ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Value ◽

Neck Squamous Cell Carcinoma ◽

Expression Levels

MicroRNAs have been proven to make remarkable differences in the clinical behaviors of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically analyze whether differential expression levels of microRNAs are related to recurrence or metastasis in patients with HNSCC. A comprehensive search of the PubMed, EMBASE, and CENTRAL was conducted up to July 24th, 2021. Data were collected and combined from studies reporting recurrence-free survival (RFS) of HNSCC patients with high microRNA expression compared to those with low expression. Besides, studies providing necessary data for evaluating the diagnostic value of microRNAs for detecting recurrence and metastasis based on their expression levels were also included and combined. The pooled hazard ratio (HR) value for the outcomes of RFS in 1,093 HNSCC samples from 10 studies was 2.51 (95%CI: 2.13–2.96). A sensitivity of 0.79 (95% CI: 0.72–0.85) and specificity of 0.77 (95%CI: 0.68–0.83) were observed in three studies, of which 93 patients with recurrence and 82 nonrecurrence controls were included, and the area under the curve (AUC) was 0.85 (95% CI: 0.81–0.88). Additionally, high diagnostic accuracy of microRNAs in detecting lymph node metastasis (LNM) was also reported. In conclusion, two panels of microRNAs showed the potential to predict recurrence or diagnose recurrence in HNSCC patients, respectively, which could facilitate prognosis prediction and diagnosis of clinical behaviors in HNSCC patients.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero), identifier CRD42020161117.

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Study on mRNA expression of Cajal body – Gemini of coiled body proteins in head and neck squamous cell carcinoma

International Journal of Molecular and Immuno Oncology ◽

10.25259/ijmio_6_2020 ◽

2020 ◽

Vol 5 ◽

pp. 108-116

Author(s):

Rooban Thavarajah ◽

Jospeh Imaneul ◽

Elizabeth Joshua ◽

Umadevi Krishnamohan Rao ◽

Kannan Ranganathan

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Tobacco Use ◽

Squamous Cell ◽

Tp53 Mutation ◽

Statistical Significance ◽

Neck Squamous Cell Carcinoma ◽

Cajal Body ◽

Mrna Levels

Objectives: The role of proteins of Cajal bodies (CB) and its identical twin, Gemini of coiled bodies (GEMs) in maintaining genomic integrity and its influence on the initiation, progression, and prognosis of head and neck squamous cell carcinoma (HNSCC) is gaining attention. We attempted to identify the CB and GEM-associated proteins (CB-GEMs) expression in HNSCC patients and study the influence of gender, TP53 mutation, age, and tobacco use on such expression. Material and Methods: TP53 mutation, tobacco use, gender, and mRNA levels of CB-GEM proteins of 520 HNSCC cases were collected and subjected to differential expression (DE) analysis. The resultant DE genes were used to create a transcriptional factor gene network using encode chip sequential data. Pathway analysis of the network was performed and presented. P ≤ 0.05 was taken as significant. Results: For smoking, the genes GEMIN8, FMR1, TRIM22, and FBL emerged as significantly DE genes. For gender, EAF1, GEMIN8, ZC3H8, TRIM22, FBL, LSG1, ZNF473, GMNC, GEMIN2, ISG20, Opa interacting protein 5, GMNN, and CDK2 were DE gene with statistical significance. For TP53, 15 genes were DE with statistical significance. Transcriptional misregulation in cancer was the frequently affected pathway. The CB-GEM bodies are effective highly conserved, splicesomal organelles that are needed for proper mRNA assembly. Certain mRNA of proteins of the CB-GEM bodies is influenced by TP53 status, gender, and tobacco use. Conclusion: The DE of CB-GEM bodies related protein in HNSCC patients are presented. Furthermore, we identified certain critical pathways, where the DE genes of CB-GEM bodies exert critical influence on HNSCC characteristics. This could potentially alter the HNSCC progression, treatment response, and prognosis.

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