Dataset Information

AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck.

ABSTRACT: A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan?Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.

SUBMITTER: Gu X

PROVIDER: S-EPMC6468641 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

<i>AP001056.1</i>, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck.

Gu Xiaolian X Wang Lixiao L Boldrup Linda L Coates Philip J PJ Fahraeus Robin R Sgaramella Nicola N Wilms Torben T Nylander Karin K

Cancers 20190311 3

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as p ...[more]

PMID: 30862109

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Project description:Alternative splicing (AS) is an important mechanism that is responsible for the production of protein diversity. An increasing body of evidence has suggested that out-of-control AS is closely related to the genesis and development of cancer. Systematic analysis of genome-wide AS in head and neck squamous cell carcinoma (HNSCC) has not yet been carried out, and consideration of this topic remains at the preliminary stage and requires further investigation. In this study, systemic bioinformatic analysis was carried out on the genome-wide AS events of 555 clinical HNSCC samples from the TCGA database. Firstly, we statistically analyzed the distributions of seven AS event types in HNSCC samples. Then, through univariate survival analysis, we observed the relationship between AS and the prognosis of the disease and found that 437 intersections of AS events were significantly related to overall survival. Among them, 335 cross-genes showed a high degree of consistency in the genes associated with overall survival and recurrence. The overall survival was significantly related to AS events. Besides, the frequency of overall survival-related ES events was evidently reduced, while the AP and the AT events were increased. In addition, AT events accounted for the largest proportion. Further, multiple regression model analysis proved that AS could become a new classification method for HNSCC, and KEGG enrichment analysis proved that most genes and proteins interacting with AS events had different biological functions and were associated with a variety of diseases. Finally, through the selection of characteristic HNSCC genes and the construction of a prognostic model, seven cross-genes related to survival and recurrence were screened out, and these characteristic genes were verified by multivariate survival model analysis so as to classify the prognosis at different splicing times and gene expression levels. These results have laid a solid foundation for our further research and play a decisive role in showing the correlation of AS with the prognosis of HNSCC.

Project description:Background:Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. Methods:The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. Results:A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR?=?3.69, 95% CI 2.73-4.98, P?<?0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR?=?1.84, 95% CI 1.21-2.81, P?<?0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR?=?3.62, 95% CI 2.58-5.09, P?<?0.001), and in the validation cohort (HR?=?1.73, 95% CI 1.12-2.67, P?=?0.014). The IFN-? response, the IFN-? response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P?<?0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P?<?0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P?<?0.01). Conclusion:Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

Project description:BackgroundFerrogenesis was strongly associated with tumorigenesis and development, and activating the ferrogenic process was a novel regimen in treating cancer, especially conventional treatment-resistant cancers. The purpose of the article was to construct a ferroptosis-related long noncoding RNAs (FRlncRNAs) signature, regardless of expression levels to effectively predict prognosis and immunotherapeutic response for head and neck squamous cell carcinoma (HNSCC).MethodsThe RNA-seq data for HNSCC and corresponding clinical information were obtained in the TCGA database, and ferroptosis-related genes (FRGs) were extracted in the ferroptosis database. On this basis, differentially expressed FRlncRNAs (DEFRlncRNAs) pairs were identified through coexpression analysis, differential expression analysis, and a fresh pairing algorithm. Then, a risk assessment model was established with univariate Cox, LASSO, and multivariate Cox regression analysis. Finally, we evaluated the model from various aspects, including survival status, clinicopathological characteristics, infiltration status of immune cells, immune functions, chemotherapeutic sensitivity, immune checkpoint inhibitors (ICIs)-related molecules, and N6-methyladenosine (m6A) mRNA status.ResultWe established a signature of 11-DEFRlncRNA pairs related to the prognosis of HNSCC that had AUC values above 0.75 in the one-, three-, and five-year ROC curves, underscoring the high susceptibility and specifiability of predicting HNSCC prognosis. Survival rates were remarkably higher for the low-risk patients than for the high-risk patients, and the signature was significantly correlated with survival, clinical, T, and N stages. Finally, immune cell infiltration status, immune functions, chemotherapeutic sensitivity, and expression levels of ICIs-related and m6A-related molecules were statistically different among different groups.ConclusionOur study established a novel lncRNA signature, which is independent of specific expression levels, could predict patient prognosis, and might have promising clinical applications in HNCSS.

Dataset Information

AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck.

Publications

<i>AP001056.1</i>, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck.

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