Prognostic Value And Tumor Immune Landscape Of M7G-related LncRNAs In Predicting Prognosis In Head And Neck Squamous Cell Carcinoma Patients

Objective: Long non-coding RNAs(lnc RNAs)play an increasingly important role in development and prognosis of tumors,and they have great potential as biomarkers of tumors.N7-methylguanosine(m7G)is a newly identified RNA modification pattern.However,the role of m7G-related lnc RNAs in head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,we sought to determine if m7G-related lnc RNAs could be used as biomarkers of prognosis and tumor microenvironment in HNSCC patients.Methods: We performed a comprehensive analysis of gene expression levels and clinical information from 522 HNSCC tissue specimens and 44 paracancer specimens from The Cancer Genome Atlas(TCGA)database.Univariate,multifactorial COX regression analyses and lasso COX regression analyses were used to build a risk model for m7G-related lnc RNAs,and the risk model was validated using Receiver operator characteristic curve(ROC)and C-index.We implemented nomogram to assess the capacity of this prediction model to predict the HNSCC prognosis.Potential functional differences between patients in different risk groups were identified by GSEA enrichment analysis,and immune characteristics of HNSCC were revealed by CIBERSORT and ESTIMATE algorithms.Finally,human pharyngeal squamous cell carcinoma cell(Fa Du)line was used to silence the m7G-related gene EIF3 D to verify the expression level of lnc RNA.Results:Eight m7G-related lnc RNAs(CASK-AS1,AC106820.5,GSEC,ALMS1-IT1,TRBV11-2,AP001020.3,AC006064.3,AL021391.1)that were significantly associated with prognosis were screened by multifactorial COX regression,and risk models were established based on these eight lnc RNAs.The risk model has promising predictive properties for the prognosis of HNSCC patients and was confirmed by the validation cohort and the total cohort.Survival rates were significantly higher in the low-risk group than in the high-risk group.The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)of the risk model was 0.707,0.770,and 0.781 for 1,3,and 5 year survival predictions for HNSCC patients,respectively.Gender,tumor stage and risk score are relevant factors in the prognosis of HNSCC,with risk score being an independent prognostic factor affecting the survival of HNSCC patients.Further immunocorrelation analysis showed that patients in the low-risk group exhibited abundant immune cell infiltration and responded well to immunotherapy.Fa Du cell RNA-seq analysis showed that 214 lnc RNAs were analyzed to be differentially expressed in cells silencing EIF3 D compared to EIF3 D normal expressing cells,of which 113 lnc RNAs were down-regulated and 101 were up-regulated.Both lnc RNAs associated with prognosis in the risk model(GSEC,ALMS1-IT1)were expressed elevated in EIF3D-silenced cell lines.Conclusion:m7G-related lnc RNAs may affect the prognosis of HNSCC patients by regulating the tumor immune microenvironment,and thus may be a molecular marker of prognosis and a potential therapeutic target for HNSCC patients.