| ObjectiveTo explore the independent prognostic factors of overall survival(OS)of male laryngeal squamous cell carcinoma(LSCC)patients,as well as to construct a prognostic prediction model,and to screen immune-related long non-coding RNA(lnc RNAs)for prognosis prediction in male patients with LSCC.Methods1.408 male patients with LSCC were enrolled in the study and regular follow-up was carried out to collect their clinical characteristics and survival data.Univariate and multivariate Cox regression models were adopted to assess the hazard ratio and its 95%confidence interval for factors affecting the overall risk of death in male patients with LSCC.2.Based on the results of multivariate Cox regression analysis,the independent prognostic factors of male LSCC were screened.With theβcoefficient or nomogram,the prognostic prediction model for male patients with LSCC was constructed.The prediction performance was evaluated by C-index,AIC and Brier score.3.Lnc RNAs differentially expressed in male LSCC were screened in TCGA database,and immune-related lnc RNAs were also screened.With the lnc RNAs selected from the intersection of the two steps,the prognosis analysis was further carried out,and finally the lnc RNAs with significant influence on the prognosis of laryngeal carcinoma were used for further analyses.4.The expression levels of the screened lnc RNAs in 21 pairs of male LSCC and para-cancerous tissues were verified by q RT-PCR.The correlation between the expression level of lnc RNAs in laryngeal cancer tissues and para-cancerous tissues and the clinicopathological characteristics of patients was further compared.The relation between the expression level of lnc RNAs and the prognosis of LSCC was assessed based on RMST.Results1.Multivariate analysis showed that for each additional year of age,the overall risk of death from laryngeal cancer increased 0.04-fold(95%CI:1.01,1.07).The mortality risk of those with junior high school education and those with senior high school education and above were 0.52 times(95%CI:0.28,0.96)and 0.41 times(95%CI:0.20,0.84)compared with those with primary school education or below,respectively.Compared with normal weight individuals(BMI=18.5-23.9 kg/m~2),underweight individuals(BMI<18.5 kg/m~2)had a significantly higher risk of death(HR=2.51;95%CI:1.25,5.03));Patients with stage IV had a higher overall risk of death than patients with early stage(HR=4.80;95%CI:2.56,9.00));Surgery significantly reduced the risk of death in patients with laryngeal cancer(HR=0.25;95%CI:0.11,0.57));In addition,the overall risk of death in patients with laryngeal cancer decreased 0.05 times(95%CI:0.90,1.00)for each 1 unit increase in PNI.2.Both the PI and the Nomogram based on the six independent influencing factors selected by multivariable Cox regression showed good prediction performance(Nomogram slightly better than PI),and the Nomogram showed significantly better prediction performance compared with the traditional TNM staging system(C-index was 0.762(0.700-0.824)and 0.678(0.603-0.753),respectively,P<0.05).3.Four prognostic immune-related lnc RNAs(AC004585,FAM225A,AC007611and LINC02043)could effectively predict the overall survival rate of patients with laryngeal cancer,which were screened based on TCGA database.In addition,compared with clinicopathological features,the risk score based on the 4 immune-related lnc RNAs showed significantly better prognostic predictive performance.4.The relative expression levels of AC004585,FAM225A,AC007611 and LINC02043 in laryngeal cancer tissues were higher than those in para-cancerous tissues.RMST analysis showed that RMST in the high expression group of AC004585,AC007611 and LINC02043 was significantly lower than that in the low expression group,suggesting that the expression levels of these 3 lnc RNAs were significantly associated with the overall survival rate of laryngeal cancer patients(P<0.05).However,there was no significant difference in RMST between the high FAM225A expression group and the low FAM225A expression group.Conclusions1.Age,education level,BMI,TNM stage,surgery and PNI were independent factors affecting the overall survival of patients with laryngeal cancer.2.The Nomogram established in our study has acceptable prognostic performance,and the Web-based prediction tool based on the Nomogram would be used in clinical practice for its convenience.3.Four immune-related lnc RNAs(AC004585,FAM225A,AC007611 and LINC02043)may be served as prognostic predictive markers in laryngeal cancer. |
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