Construction of prognostic signature of patients with oral squamous cell carcinoma based on pyroptosis-related long non-coding RNAs

Abstract

Background and objectiveOral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and its morbidity and mortality are increasing year by year. Changes in key genes are thought to be closely related to the occurrence and development of OSCC. Pyroptosis is an inflammatory form of programmed cell death that has been implicated in malignancies and inflammatory diseases. Changes in the expression of long noncoding RNAs may also affect tumorigenesis and progression. In this study, our main objective was to evaluate the association between pyroptosis-related lncRNAs and prognosis in patients with OSCC.MethodsThe RNA-seq data and clinicopathological data of OSCC patients are from The Cancer Genome Atlas database. The pyroptosis gene set is obtained from Gene Set Enrichment Analysis database. Univariate COX, Lasso and multivariate COX regression analyses were used for the construction of risk prognostic models of OSCC, eight lncRNAs were incorporated into prognostic models. The Kaplan-Meier method and log-rank test were used to evaluate the differences of overall survival between patients in high-risk and low-risk groups. The reliability of predictions across the dataset was analyzed by receiver operating characteristic (ROC) curves. The immune signature score was calculated using the single-sample gene set enrichment analysis.ResultsEight pyroptosis-related lncRNAs were used to construct prognostic signature of OSCC, including AC136475.2, AC024075.2, JPX, ZFAS1, TNFRSF10A-AS1, LINC00847, AC099850.3 and IER3-AS1. According to this prognostic signature, patients with OSCC were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis showed that the survival rate of the high-risk group was significantly lower than the low-risk group. ROC area for risk score was 0.716, and ROC area of the 8 lncRNAs are all between 0.5 and 1, implied that these lncRNAs had high accuracy in predicting the prognosis of OSCC patients. Immune Infiltration findings suggested that these lncRNAs affected immune responses in the microenvironment of OSCC.ConclusionThe prognostic signature based on pyroptosis-related lncRNAs potentially serves as an independent prognostic indicator for OSCC patients. And this signature facilitates research on targeted diagnosis and treatment of patients diagnosed with OSCC.

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

“…Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83], 8 studies on necroptosis [84][85][86][87][88][89][90][91] and 5 studies on other types of cell death [92][93][94][95][96]. One study [28] explored both ferroptosis and pyroptosis, Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73]…”

“…Previous findings revealed that 5-fluorouracil (5-FU) treatment increased NLRP3 expression in OSCC, which mediated drug resistance. It was also proven Methods of pyroptosis inhibition are gaining the attention of the scientific community [65,69,74,154]. Yang et al [69] highlighted that extracellular vesicles derived from bitter melon led to a significant decrease in the expression of NLRP3, reducing OSCC resistance to 5-FU treatment.…”

“…The pro-inflammatory environment can also contribute to resistance to therapy and promote angiogenesis, which is the formation of new blood vessels that supply nutrients to the tumor. The study developed by Xin et al [74] used The Cancer Genome Atlas (TCGA) dataset to investigate the predictive value of pyroptosis-related lncRNAs in the prognosis of OSCC. The authors identified eight pyroptosis-related lncRNAs associated with overall survival in patients with OSCC by multivariate regression analysis.…”

“…However, the studies highlighted the potential of pyroptosis in the control of OSCC development and progression and described drugs and molecules related to both blockage and induction of it. Moreover, two studies demonstrated that pyroptosis gene clusters are correlated with clinical characteristics, infiltration of immune cells, susceptibility to chemotherapy and immunotherapy, and prognosis of patients with OSCC [74,75]. It will be important to validate these risk models and to explore potential drugs that could induce cell death through pyroptosis and concomitantly inhibit the pro-tumor inflammatory response in OSCCs.…”

Prognostic model revealing pyroptosis-related signatures in oral squamous cell carcinoma based on bioinformatics analysis

“…It was reported that a pyroptosis-related gene signature was prognostic for HNSC patient 13 . Several recent studies performed bioinformatics analyses and found that the pyroptosis-related signature was prognostic for the level of immune cell infiltration benefit to immunotherapies in OSCC 14 – 16 . Other evidences were also provided about the role of pyroptosis in the development and treatment of OSCC 17 , 18 .…”