ObjectiveLocoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients.Materials and methodsHistologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan–Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored.ResultsOur nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p<0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients.ConclusionsOur OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.

Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N6-methyladenosine (m6A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of head and neck squamous cell carcinoma. Thus, combining indicated that immune-related gene prognostic index with m6A status should offer a better predictive power for immune responses.Methods: Head and neck squamous cell carcinoma samples from the cancer genome atlas (TCGA, n = 498) and gene expression omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the indicated that immune-related gene prognostic index through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m6A risk score was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to tumor immune microenvironment cell-infiltrating characteristics.Results: A composite score was determined based on indicated that immune-related gene prognostic index and m6A risk score. Head and neck squamous cell carcinoma patients in the cancer genome atlas were divided into four subgroups: A (IRGPI-High&m6A-risk-High, n = 127), B (IRGPI-High&m6A-risk-Low, n = 99), C (IRGPI-Low&m6A-risk-High, n = 99), and D (IRGPI-Low&m6A-risk-Low, n = 128), and overall survival (OS) was significantly different between subgroups (p < 0.001). The characteristics of tumor immune microenvironment cell infiltration in the four subgroups were significantly different in subgroups (p < 0.05). The receiver operating characteristic (ROC) curves show the predictive value of composite score for overall survival was superior to other scores.Conclusion: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for head and neck squamous cell carcinoma.

Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N6-methyladenosine (m6A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of HNSCC. Thus, combining IRGPI with m6A status should offer a better predictive power for immune responses.Methods: HNSCC samples from The Cancer Genome Atlas (TCGA, n=498) and Gene Expression Omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the IRGPI through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m6A risk score was constructed by least absolute shrinkage and selection operator regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to TIME cell-infiltrating characteristics.Results: A composite score was determined based on IRGPI and m6A risk score. HNSCC patients in the TCGA were divided into four subgroups：A (IRGPI-High&m6A-risk-High, n=127), B (IRGPI-High&m6A-risk-Low, n=99), C (IRGPI-Low&m6A-risk-High, n=99) and D (IRGPI-Low&m6A-risk-Low, n=128), and overall survival (OS) was significantly different between subgroups (P < 0.001). The characteristics of TIME cell infiltration in the four subgroups were significantly different in subgroups (P < 0.05). The ROC curves show the predictive value of composite score for OS was superior to any other scores.Conclusions: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for HNSCC.