Dataset Information

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

ABSTRACT: Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient's biology and outcome. We found that WPS can induce the epithelial-mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan-Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients' survival.

SUBMITTER: Lopez-Ozuna VM

PROVIDER: S-EPMC7560251 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

López-Ozuna Vanessa M VM Gupta Ishita I Kiow Ryan Liu Chen RLC Matanes Emad E Kheraldine Hadeel H Kheraldine Hadeel H Yasmeen Amber A Khalil Ashraf A Vranic Semir S Al Moustafa Ala-Eddin AE Farsi Halema F Al HFA

Toxics 20200918 3

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are sti ...[more]

PMID: 32961854

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Project description:Head and neck cancer is the sixth most common malignancy around the world, and 90% of cases are squamous cell carcinomas. In this study, we performed a systematic investigation of the immunogenomic landscape to identify prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC). We analyzed the expression profiles of immune-related genes (IRGs) and clinical characteristics by interrogating RNA-seq data from 527 HNSCC patients in the cancer genome atlas (TCGA) dataset, including 41 HPV+ and 486 HPV- samples. We found that differentially expressed immune genes were closely associated with patient prognosis in HNSCC by comparing the differences in gene expression between cancer and normal samples and performing survival analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of the differentially expressed immunogenomic prognosis-related genes. Two additional cohorts from the Oncomine database were used for validation. 65, 56 differentially expressed IRGs was associated with clinical prognosis in total and HPV- samples, respectively. Furthermore, we extracted 10, 11 prognosis-related IRGs from 65, 56 differentially expressed IRGs, respectively. They were significantly correlated with clinical prognosis and used to construct the prognosis prediction models. The multivariable ROC curves (specifically, the AUC) were used to measure the accuracy of the prognostic models. These genes were mainly enriched in several gene ontology (GO) terms related to immunocyte migration and receptor and ligand activity. KEGG pathway analysis revealed enrichment of pathways related to cytokine-cytokine receptor interactions, which are primarily involved in biological processes. In addition, we identified 63 differentially expressed transcription factors (TFs) from 4784 differentially expressed genes, and 16 edges involving 18 nodes were formed in the regulatory network between differentially expressed TFs and the high-risk survival-associated IRGs. B cell and CD4 T cell infiltration levels were significantly negatively correlated with the expression of prognosis-related immune genes regardless of HPV status. In conclusion, this comprehensive analysis identified the prognostic IRGs as potential biomarkers, and the model generated in this study may enable an accurate prediction of survival.

Project description:Squamous cell carcinoma of the head and neck (HNSCC) is one of the six most common malignancies. HNSCC has both a high incidence and poor prognosis, and its prognostic factors remain unclear. Ferroptosis is a newly discovered form of programmed cell death that is iron-dependent. Increasing evidence indicates that targeting ferroptosis may present a new form of anti-tumor treatment. However, the prognostic value of ferroptosis-related genes (FRGs) in HNSCC is unclear. This study was designed to identify molecular markers associated with ferroptosis that influence prognosis in patients with HNSCC. We used HNSCC tumor and normal data from The Cancer Genome Atlas (TCGA) to identify prognosis-related FRGs. An FRG-based prognostic risk score was constructed, and its prognostic value for patients with HNSCC was evaluated using receiver operating characteristic curve (ROC) and nomogram analyses. The model was validated using the Gene Expression Omnibus (GEO) database. Univariate Cox regression analysis in patients with HNSCC revealed 11 FRGs that were significantly associated with overall survival (OS). We constructed a ferroptosis risk score model based on five genes and divided the patients into different risk groups based on its median value. Kaplan-Meier curve analysis showed that patients with a higher ferroptosis risk score had shorter OS (TCGA training set: P < 0.001, TCGA validation set: P < 0.05,GEO validation set: P < 0.001), and Gene Expression Profiling Interactive Analysis (GEPIA) further verified the relationships between these five genes and prognosis in patients with HNSCC. Multivariate Cox regression analysis showed that the risk score remained an independent predictor of OS after the exclusion of clinical confounders (HR > 1, P < 0.01). Significant differences in gene function enrichment analysis and immune cell infiltration status were identified between the two groups. The prognostic model can be used to predict the prognosis of patients with HNSCC. Moreover, the five FRGs may affect ferroptosis in HNSCC and thereby represent potential treatment targets. These results provide new directions for HNSCC treatment.

Project description:BackgroundWater pipe smoking has become a global public health problem as its popularity increased over time, especially among youth. The objective of our study was to estimate water pipe tobacco smoking prevalence and to assess socioeconomic factors associated with ever water pipe smoking by public and private university students in Ankara, Turkey.MethodsThis descriptive study was based on a survey conducted among public (n=2685) and private (n=2485) university students via an online questionnaire on demographics and water pipe consumption patterns. For every student in the sample, a socioeconomic status index was calculated using principal component analysis. Binary logistic regressions for the outcome variable of ever-using water pipe yielded estimates of adjusted odds ratios (aORs) for the associated factors such as the respondent's age, gender, university type, and socioeconomic status.ResultsThe prevalence of ever use of water pipe was 69.1% (95% CI: 67.2-70.9%) among private and 59.1% (95% CI: 57.2-60.9%) among public university students. A substantial share of ever users were current users (25.5% in private versus 21.6% in public, p=0.008). On average, private university students had higher socioeconomic status than public university students (for example, access to a car (51.7% versus 35.8%, p=0.008), financial support from family (71.5% versus 65.1%, p<0.001)), also demonstrated by a higher socioeconomic status index. Being a private university student (aOR 1.57, 95% CI: 1.38-1.79), older (aORs 1.50 to 2.39, p<0.001), male (aOR 2.36, 95% CI:2.06-2.70), as well as having greater financial resources, such as having access to a car (aOR 1.24, 95% CI:1.07-1.42), or having income support from family (aOR 1.32, 95% CI:1.13-1.54), were associated with ever-using water pipe. A higher SES index was significantly associated with higher odds of ever using water pipe among both private (aOR 1.13, 95% CI:1.06,1.20) and public university (aOR 1.12, 95% CI:1.06,1.19) students.ConclusionsWater pipe smoking was common in both public and private universities; however, private university students had higher odds of ever using water pipe. There is an urgent need to implement evidence-based interventions, taking into account the socioeconomic status of young adults, to prevent them from water pipe smoking.

Project description:BackgroundChronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC.MethodsMethylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival.ResultsThe mean number of methylated genes per sample was 2.05 ± 2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5-9 methylated genes had a significantly lower survival rate than that of patients with 0-4 methylated genes (log-rank test, P= 0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P = 0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P = 0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P = 0.028 and P = 0.006, respectively). Moreover, Patients with 5-9 methylated genes were extremely lower of 5hmC levels (P = 0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P < 0.05 and P < 0.05, respectively).ConclusionWe characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.

Dataset Information

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

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Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

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