| Part Ⅰ:Bioinformatics analysis of prognostic factors in HNSCCCTMEM173 Is a Prognostic Biomarker and Recruit Tumor Infiltrating Lymphocyte in Squamous cell carcinoma of Head and Neck CancersPurpose:TMEM173 gene is an innate immune regulatory gene.The protein encoded by TMEM173 is an occasional facilitator of innate immune signaling that acts as a sensor of cytosolic DNA and promotes the production of type Ⅰ interferon.While it can exert an effect on oncotherapy and prognosis in several cancers,further bioinformatics analysis in head and neck cancer(HNSCC)has yet to be performed.We aimed to explore the expression and prognostic values of TMEM173 in H-NSCC,and its relationship with HPV P16/CDKN2A gene.The regulatory function of TMEM173 in immunity and other pathways was also investigated.Materials and methods:The data used for analysis was mainly from TCGA dataset.The online analysis tools,including GEPIA,Reactome Pathway Database,and KM plotter database,UCSC Xena browser and cBioPortal for Cancer Genomics database,were used for the analysis of gene expression,tumor infiltrating lymphocyte and survival prognosis.Results:We observed that TMEM173 expression was not significantly elevated in HNSCC tissues,but its expression was higher in HPV-positive HNSCC compared with HPV-negative HNSCC.The expression of TMEM173 could recruit tumor infiltrating lymphocyte.Furthermore,TMEM173 involved in multiple functional regulations and its expression was regulated by p16/CDKN2A gene,apoptosis-and autophagy-related genes.Higher expression of TMEM173 correlated with a favorable OS(HR=0.72,p=0.021)in HNSCC patients.Conclusion:Above all,TMEM173 involved in recruiting tumor infiltrating lymphocytes in the tumor microenvironment and high expression of TMEM173 predicted favorable OS of HNSCC patients,recommending it as a promising therapeutic target.Part Ⅱ:Explore the treatment model of primary squamous cell carcinoma of parotid gland based on SEER databaseTitle 1:Predictive Nomogram and associations with survival improvement benefit from postoperative radiotherapy for the squamous cell carcinoma of parotid gland.Purpose:Squamous cell carcinoma of parotid gland(parotid SCC)is a rare pathological type of parotid carcinomas.Most of the prognostic indicators treatment analysis for parotid SCC are mainly available through small retrospective studies.Postoperative radiotherapy(PORT)is recommended for the treatment of parotid SCC,which clinical benefit needs further evaluation based on the risk stratification model.Materials and methods:A retrospective cohort was performed to analyze patients with parotid SCC treated with surgery between 1975-2016 in Surveillance,Epidemiology,and End Results database.Patients were divided into surgery+RT(RT group)and surgery alone(non-RT group).A predictive Nomogram model was constructed to stratify patients based on the risk factors of 5-year overall survival(OS).The benefit value of PORT was evaluated by Cox regression model between two groups.Results:A total of 581 patients with parotid SCC was identified,403(69.4%)in RT group and 178(30.6%)in non-RT group.Over a median follow-up of 72 months,310(53.4%)deaths occurred,with 106(59.6%)deaths in non-RT group and 204(50.6%)deaths in RT group.The predictive Nomogram risk model was more accurate and useful or stratifying OS and clinical decisions than other staging systems.Compared with non-RT group,significant survival improvements in the RT group in medium risk level(HR=0.638,95%CI=0.482-0.844,P=0.002),and the survival benefit was absent in patients with low and high risk.Conclusion:Our study demonstrates that age,T stage and the number of positive nodes is independent factors for 5-year OS.The predictive Nomogram model can better stratify the prognosis of patients with parotid SCC,and further screen patients benefiting from PORT,suggesting that this model could serve as a decision reference for PORT to avoid overtreatment.Part Ⅱ:Explore the treatment model of primary squamous cell carcinoma of parotid gland based on SEER databaseTitle 2:The efficacy of radiotherapy and chemotherapy for squamous cell carcinoma of parotid gland:analysis from a population-based studyPurpose:Primary squamous cell carcinoma of parotid gland(primary parotid SCC)is a rare parotid cancer.The survival benefit of radiotherapy(RT)and chemotherapy(CT)based on risk factors for cancer-specific survival(CSS)and overall survival(OS)need further evaluated.Materials and methods:We performed a retrospective cohort study to identify patients with primary parotid SCC diagnosed between 1975 and 2016 by using SEER data.Patients were divided into five groups:S alone,S+RT,S+CRT,RT alone,CRT.We stratified patients based on the risk factors by Cox multivariable analysis,and the comprehensive comparison was performed using univariable,multivariable,and propensity score-matched analyses.Results:We identified 2324 eligible patients with primary parotid SCC,and 1172 patients had clear stages.Within the median follow-up of 107 months,postoperative patients had better survival than nonoperative patients.PORT significantly improved the OS for postoperative patients(HR=0.778,95%CI=0.652-0.927,P=0.005).In the risk-adapted analysis based on age,tumor and nodal stage,patients receiving PORT had a better OS compared with surgery alone in high-risk groups(41.1 vs.27.4,P=0.002),while the survival wasn’t improved by chemotherapy.Nonoperative patients receiving chemoradiotherapy had a better OS tendency than radiotherapy alone(HR=0.778,95%CI=0.652-0.927,P=0.005),and age,tumor stage were prognostic factors of OS.After adjustment,the similar significant differences in OS and CSS were observed.Conclusion:PORT could significantly improve the OS of postoperative patients,and nonoperative patients treated with CRT had a better OS than RT.Risk-adapted treatment stratifies is viable and effective for patients.Part Ⅲ:The analysis of nasopharyngeal carcinoma prognosisTitle:The prognosis of nasopharyngeal carcinoma and construction of prognostic risk modelPurpose:Due to the heterogeneity of tumors,the overall survival(OS)of nasopharyngeal carcinoma patients,even those with the same clinical stage,is significantly different among different tumors,and the treatment guided by TNM staging alone is still not perfect.We attempted to develop a more comprehensive and accurate prognostic evaluation model to individualize the prognosis of patients with non-metastatic nasopharyngeal carcinoma through risk stratification.Materials and methods:We collected the first diagnosis of non-metastatic nasopharyngeal carcinoma patient’s diagnosis and treatment of information between August 2003 and May 2017 in the China National Cancer Center,the Cancer Hospital of the Chinese Academy of Medical Sciences:age,T stage,N stage,Epstein-Barr virus(EBV)DNA level,serum lactate dehydrogenase(LDH)level,history of smoking and drinking alcohol,and all the eligible patients received radical radiotherapy.The primary focus of the study was overall survival(OS),and the secondary endpoints were progression-free survival(PFS),local-regional progression-free survival(LRPFS),and distant metastasis-free survival(DMFS).Based on the independent prognostic factors for OS derived from multivariate Cox proportional risk regression,we constructed a prognostic risk model and divided patients into four risk levels.The predictive ability and accuracy of the risk prognosis model were evaluated by C index and calibration plot.Kaplan-Meier method was used to perform OS,PFS,LRPFS and DMFS of each risk group,and log-rank was used to test the differences between groups.Results:1,872 patients were eventually enrolled,of whom 1,374(73.4%)were male,with a median age of 47 years(range 4-82 years).Based on six independent prognostic factors obtained from Cox multivariate analysis:age,T stage,N stage,smoking history,EBV DNA and LDH as independent prognostic factors for OS,we constructed a prognostic risk model for non-metastatic nasopharyngeal carcinoma.Prognostic risk models were significantly better than the 8th edition AJCC TNM staging system in predicting outcomes(OS,PFS,LRPFS,and DMFS).The correction curves of OS,PFS,LRPFS and DMFS of the risk model we constructed were in good agreement with the actual prognosis,which was better than that of AJCC staging system.According to the prognostic risk model,we divided the speech into four risk levels:risk group 1(0-1 risk factors),risk group 2(2 risk factors),risk group 3(3 risk factors),and risk group 4(4-6 risk factors).The four risk stratifications of OS(P<0.001),PFS(P<0.001),LRPFS(P<0.001)and DMFS(P<0.001)showed a good degree of differentiation,especially the OS and PFS of the four risk groups,with significant differences between groups.The 5-year OS of the four risk groups was 92.5%,85.5%,80.1%,59.1%,(P<0.001)and 5-year PFS was 86.7%,79.9%,69.4%,and 52.1%(P<0.001),respectively.Conclusion:Patients were classified into four risk levels by prognostic risk factor scoring,and these four risk groups showed significant differences in survival,prognosis,and disease control.Through this model,oncologists can accurately and effectively evaluate the prognosis of patients,and make more reasonable clinical decisions and recommendations for review and follow-up. |
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