Development of a novel prognostic signature derived from enhancer RNA-regulated genes in head neck squamous cell carcinoma.

Enhancer RNAs (eRNAs) are increasingly recognized as prognostic biomarkers-across human cancers. Here, we sought to develop a novel eRNA-regulated genes (ERGs)-derived prognostic signature for head neck squamous cell carcinoma (HNSCC). Candidate ERGs were identified via co-expression between individual survival-related eRNAs and their putative targets by Spearman's correlation analyses. The ERG signature was developed by univariate Cox regression, Kaplan-Meier survival analysis and maximum AUC in 1000 iterations of LASSO-penalized multivariate Cox regression. An ERG nomogram incorporating ERG signature and selected clinicopathological parameters were constructed by multivariate Cox regression. Biological roles of eRNA of interest were further explored in vitro. The ERG signature successfully stratified patients into subgroups with distinct survival in multiple cohorts. An ERG nomogram was developed with satisfactory performance in prognostication. Inhibition of ENSR00000165816 significantly reduced transcript level of SLC2A9 and impaired cell proliferation and invasion. Our results establish ERG signature and nomogram as powerful prognostic predictors for HNSCC.

Diao P ，Huang R ，Shi Y ，Yao Q ，Dai Y ，Yuan H ，Wang Y ，Cheng J ... -  《-》

Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for head and neck squamous cell carcinoma.

Mao R ，Chen Y ，Xiong L ，Liu Y ，Zhang T ... -  《Aging-US》

A pyroptosis-related lncRNA signature predicts prognosis and immune microenvironment in head and neck squamous cell carcinoma.

Pyroptosis, a type of regulated cell death controlled by the gasdermin family of proteins to form plasma membrane pores is known. Nonetheless, the function of pyroptosis-related long non-coding RNAs (lncRNAs) in this process still lacks exhaustive elucidation in head and neck squamous cell carcinoma (HNSCC). Other attributes encompassing the function of such lncRNAs in the immune microenvironment and potential prognosis for HNSCC are yet to see the light of the day. This work was designed to probe the possible prognostic worth of pyroptosis-related lncRNAs along with their impact on the immune microenvironment in the case of HNSCC. The Cancer Genome Atlas (TCGA) database was the source of RNA-sequencing data of HNSCC patients. Pearson correlation analysis was employed to scour for lncRNAs linked to pyroptosis based on 40 genes related to the process. Following the construction of a pyroptosis-related lncRNA signature employing univariate, Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, survival and nomogram analyses ensued to scrutinize the predictive value of the prognostic signature. The segregation of patients into two risk groups was done by the constructed pyroptosis-related-lncRNA signature (encompassing 14 lncRNAs). The prognosis was poorer for individuals of the high-risk group versus (vs.) the low-risk group with the risk score emerging as an independent prognostic factor by regression analyses. The accuracy of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the three-years area under time-dependent ROC curve (AUC) reaching 0.767. Further analyses unveiled a conspicuous enrichment of immune-related pathways in the low-risk group. The high-risk group demonstrated an immunologically "cold" profile based on the immune cell infiltration landscape. The lncRNA signature encompassing 14 pyroptosis-related lncRNAs could be a prognostic marker for HNSCC, suggesting pyroptosis might be a promising therapeutic target in HNSCC.

Zhu W ，Ye Z ，Chen L ，Liang H ，Cai Q ... -  《-》

Identification of 4-lncRNA prognostic signature in head and neck squamous cell carcinoma.

Deregulated long noncoding RNAs (lncRNA) have been critically implicated in tumorigenesis and serve as novel diagnostic and prognostic biomarkers. Here we sought to develop a prognostic lncRNA signature in patients with head and neck squamous cell carcinoma (HNSCC). Original RNA-seq data of 499 HNSCC samples were retrieved from The Cancer Genome Atlas database, which was randomly divided into training and testing set. Univariate Cox regression survival analysis, robust likelihood-based survival model and random sampling iterations were applied to identify prognostic lncRNA candidates in the training cohort. A prognostic risk score was developed based on the Cox coefficient of four individual lncRNA imputed as follows: (0.14546 × expression level of RP11-366H4.1) + (0.27106 × expression level of LINC01123) + (0.54316 × expression level of RP11-110I1.14) + (-0.48794 × expression level of CTD-2506J14.1). Kaplan-Meier analysis revealed that patients with high-risk score had significantly reduced overall survival as compared with those with low-risk score when patients in training, testing, and validation cohorts were stratified into high- or low-risk subgroups. Multivariate survival analysis further revealed that this 4-lncRNA signature was a novel and important prognostic factor independent of multiple clinicopathological parameters. Importantly, ROC analyses indicated that predictive accuracy and sensitivity of this 4-lncRNA signature outperformed those previously well-established prognostic factors. Noticeably, prognostic score based on quantification of these 4-lncRNA via qRT-PCR in another independent HNSCC cohort robustly stratified patients into subgroups with high or low survival. Taken together, we developed a robust 4-lncRNA prognostic signature for HNSCC that might provide a novel powerful prognostic biomarker for precision oncology.

Diao P ，Song Y ，Ge H ，Wu Y ，Li J ，Zhang W ，Wang Y ，Cheng J ... -  《-》

Identification and in vitro validation of prognostic lncRNA signature in head and neck squamous cell carcinoma.

Wang J ，Bian Q ，Liu J ，Moming A ... -  《-》