Abstract
Competitive endogenous RNAs (ceRNAs) act as molecular sponges for microRNAs (miRNAs), and are associated with tumorigenesis in various cancers, including laryngeal cancer (LC). In this work, we constructed an LC-specific inflammatory gene-related ceRNA network (IceNet). In IceNet, ceRNAs targeting inflammation-related genes tended to be network hubs. Additionally, the betweenness centralities of these hub ceRNAs were higher than those of the inflammation-related genes themselves, indicating that the hub ceRNAs in this study played critical roles in communication between IceNet molecules. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that IceNet molecules are associated with multiple cancer-related functions and signaling pathways. Using cFinder software and survival analyses, we identified a potential prognostic module within IceNet that contains 18 mRNAs and a long non-coding RNA (lncRNA), and we effectively stratified patients into high- and low-risk subgroups with different survival outcomes, independent of patient age and tumor grade. This 18-mRNA and one-lncRNA module provides a novel mechanism for potentially improving LC patient prognostic predictions. Applying the module clinically to differentiate high- and low-risk patients could inform therapeutic decision making and ultimately improve patient outcomes. In addition, these results demonstrate the potential importance of IceNet hub ceRNAs in LC development and progression.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, with a mortality rate of ~50%
We found that inflammatory genes had lower degree and closeness centralities (CC) than their Competitive endogenous RNAs (ceRNAs) in the inflammatory generelated ceRNA network (IceNet) (p=2.42e-11 for degrees, Figure 2A; p=1.15e-4 for CC, Figure 2B; Wilcoxon rank sum test), indicating that inflammatory gene ceRNAs were central within IceNet
On the basis of the ceRNA hypothesis and the fact that inflammation likely promotes laryngeal cancer (LC), we used LC patient long non-coding RNA (lncRNA) and messenger RNAs (mRNAs) expression profiles combined with experimentally validated miRNA-target interactions to construct an inflammatory gene-associated ceRNA network (IceNet)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, with a mortality rate of ~50%. Radiotherapeutic, and chemotherapeutic technologies continue to improve, LC patient prognosis remains poor. Novel therapeutic targets are required to improve diagnosis and prognosis prediction, and survival outcomes, in LC patients. Recent efforts focused on the relationship between inflammatory cells and many types of cancers have revealed that inflammatory cells can occupy much of the tumor microenvironment, fostering tumor cell proliferation, survival and migration [3]. Signaling pathways that orchestrate innate inflammation, such as NF-kB, are activated in many cancers [5]. These findings provide insight into mechanisms of inflammation in promoting tumorigenesis. The present study focuses on novel LC prognostic biomarkers from the perspective of inflammation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
