Comprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment

et al. 2020

Oncol Lett

Approximately 500,000 new head and neck squamous cell carcinoma (HNSCC) cases are detected every year around the world, and its incidence ranks sixth among all cancer types globally. Among these cases, oral squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC) are HNSCC subtypes with high incidence rates, especially in China. The present study examines the association between the apolipoprotein L1 (APOL1) mRNA and protein expression and clinical parameters in HNSCC. The two most common types (oral and larynx) of HNSCC were selected for subgroup analyses. Immunohistochemistry (IHC) was used to detect APOL1 protein expression levels in HNSCC clinical specimens. It was demonstrated that APOL1 protein expression in 221 cases of HNSCC was higher compared with that in normal tissues. Consistent upregulation of APOL1 protein was also found in subgroups of OSCC and LSCC. Through mining the ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, microarrays and RNA sequencing data for HNSCC were retrieved, which were used to analyze APOL1 mRNA expression levels. The results showed that APOL1 expression was higher in both OSCC and LSCC subtypes, as well as in HNSCC, compared with that in non-cancerous squamous epithelium. The summary receiver operating characteristic analysis showed that APOL1 had potential as a diagnostic biomarker for HNSCC, OSCC and LSCC. Thus, upregulation of APOL1 may contribute to the tumorigenesis of HNSCC.

Section: Introductionmentioning

confidence: 99%

The clinical significance of apolipoprotein L1 in head and neck squamous cell carcinoma

Zhong¹,

et al. 2020

Oncol Lett

“…A study aimed at identifying AS events (ASE) in human papillomavirus (HPV)-negative HNSCC demonstrated that the analysis of ASE in HPVnegative HNSCC identified multiple changes that may be associated with carcinogenesis, including carcinogenic DOCK5 variants (52). A recent study conducting a genome-wide analysis of AS events using RNA-seq data from the TCGA program in a sample of 464 HNSC patients revealed new AS events associated with carcinogenesis and the immune microenvironment (55). Likewise, another study systematically analyzed the RNA binding protein (RBP) gene mutations, copy number, and gene expression pattern, and changes of AS in these tumors, and AS sequence enrichment and the motif of the change in cancer RBP expression (56).…”

Section: Discussionmentioning

confidence: 99%

Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma

Wei

et al. 2020

Front. Oncol.

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 Li et al.RNA Alternative Splicing Signals in HNSCC 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.

“…Although the identification, screening and clinical use of neoantigens still face various challenges, neoantigens with tumor tissue specificity and high immunogenicity are expected to benefit more patients as potential targets for cellular immunotherapy [31,32]. Previously, TCGA as the principal guide to understanding of the complex tumor biology [33], large-scale sequencing data were used to identify prognostic AS events and revealed pathogenesis through regulatory splicing networks in colorectal cancer and head-neck carcinoma [34,35]. More and more AS-related prognostic models have been established, showing excellent efficacy in various cancers.…”

Section: Discussionmentioning

confidence: 99%

Clusterization in acute myeloid leukemia based on prognostic alternative splicing signature to reveal the clinical characteristics in the bone marrow microenvironment

Zhang

et al. 2020

Cell Biosci

Background Alternative splicing (AS), a crucial post-transcriptional regulatory mechanism in expanding the coding capacities of genomes and increasing the diversity of proteins, still faces various challenges in the splicing regulation mechanism of acute myeloid leukemia (AML) and microenvironmental changes. Results A total of 27,833 AS events were detected in 8337 genes in 178 AML patients, with exon skip being the predominant type. Approximately 11% of the AS events were significantly related to prognosis, and the prediction models based on various events demonstrated high classification efficiencies. Splicing factors correlation networks further altered the diversity of AS events through epigenetic regulation and clarified the potential mechanism of the splicing pathway. Unsupervised cluster analysis revealed significant correlations between AS and immune features, molecular mutations, immune checkpoints and clinical outcome. The results suggested that AS clusters could be used to identify patient subgroups with different survival outcomes in AML, among which C1 was both associated with good outcome in overall survival. Interestingly, C1 was associated with lower immune scores compared with C2 and C3, and favorable-risk cytogenetics was rarely distributed in C2, but much more common in C1. Conclusions This study revealed a comprehensive landscape of AS events, and provides new insight into molecular targeted therapy and immunotherapy strategy for AML.