scholarly journals PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 762
Author(s):  
Magda Kopczyńska ◽  
Tomasz Kolenda ◽  
Kacper Guglas ◽  
Joanna Sobocińska ◽  
Anna Teresiak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Hpv Infection ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Potential Biomarker

Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
Xiliang Zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Using Data ◽  
Low Expression

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

scholarly journals The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanying Feng ◽  
Feifei Xue ◽  
Yingzheng He ◽  
Tianxiao Wang ◽  
Hua Yuan
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Network Analysis ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Score Model

ObjectivesThis study aimed to identify genes regulating cancer stemness of head and neck squamous cell carcinoma (HNSCC) and evaluate the ability of these genes to predict clinical outcomes.Materials and MethodsThe stemness index (mRNAsi) was obtained using a one-class logistic regression machine learning algorithm based on sequencing data of HNSCC patients. Stemness-related genes were identified by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis (LASSO). The coefficient of LASSO was applied to construct a diagnostic risk score model. The Cancer Genome Atlas database, the Gene Expression Omnibus database, Oncomine database and the Human Protein Atlas database were used to validate the expression of key genes. Interaction network analysis was performed using String database and DisNor database. The Connectivity Map database was used to screen potential compounds. The expressions of stemness-related genes were validated using quantitative real‐time polymerase chain reaction (qRT‐PCR).ResultsTTK, KIF14, KIF18A and DLGAP5 were identified. Stemness-related genes were upregulated in HNSCC samples. The risk score model had a significant predictive ability. CDK inhibitor was the top hit of potential compounds.ConclusionStemness-related gene expression profiles may be a potential biomarker for HNSCC.

scholarly journals The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Yongping Zhang ◽  
Chaojie Liang ◽  
Yu Zhang ◽  
Zhinmin Wang ◽  
Ruihuan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Patients ◽  
Tumor Size ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Tnm Stage ◽  
Potential Biomarker ◽  
Tcga Dataset

Abstract Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

scholarly journals Functions and Clinical Significance of KLRG1 in the Development of Lung Adenocarcinoma and Immunotherapy

2020 ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
xiliang zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Killer Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Normal Lung ◽  
Using Data ◽  
Low Expression

Abstract Background. As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 in lung adenocarcinoma (LUAD) after immune-checkpoint inhibitor therapy, as well as to explore the role of a possible KLRG1 molecular mechanism on LUAD development.Methods. Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We further established a stable LUAD cell line with KLRG1 knockdown and investigate the effect of KLRG1 knockdown on tumor cell proliferation. We also studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy.Results. The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 tumor cells. And low expression of these four factors was all associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses in LUAD patients after immunotherapy.Conclusion. Based on these findings, we infer that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD. Key pointsKLRG1 inhibits the progress of LUAD.KLRG1 had significant correlation with immunotherapy response.KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

scholarly journals Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

2020 ◽  
pp. 1-10
Author(s):  
George Wilson ◽  
Jessica D. Arden ◽  
Thomas J. Quinn ◽  
Thomas G. Wilson ◽  
Alaa Hanna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Automated Quantification ◽  
Control Disease ◽  
Disease Free

This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

scholarly journals The role of miR-92b in cholangiocarcinoma patients

2018 ◽  
Vol 33 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Min-hang Zhou ◽  
Hong-wei Zhou ◽  
Mo Liu ◽  
Jun-zhong Sun
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Positive Regulation ◽  
Cancer Genome Atlas ◽  
High Level ◽  
Genome Atlas

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

scholarly journals Synthetic Evaluation of MicroRNA-1-3p Expression in Head and Neck Squamous Cell Carcinoma Based on Microarray Chips and MicroRNA Sequencing

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Yubing Chen ◽  
Mingjiang Liu ◽  
Hu Jin ◽  
Bo Peng ◽  
Luo Dai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Regulatory Pathways

Background. MicroRNA-1-3p (miR-1-3p) exerts significant regulation in various tumor cells, but its molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) are still ill defined. This study is aimed at detecting the expression of miR-1-3p in HNSCC and at determining its significant regulatory pathways. Methods. Data were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, ArrayExpress, Sequence Read Archive (SRA) databases, and additional literature. Expression values of miR-1-3p in HNSCC were analyzed comprehensively. The R language software was employed to screen differentially expressed genes, and bioinformatics assessment was performed. One sequence dataset (HNSCC: n = 484 ; noncancer: n = 44 ) and 18 chip datasets (HNSCC: n = 656 ; noncancer: n = 199 ) were obtained. Results. The expression of miR-1-3p in HNSCC was visibly decreased in compare with noncancerous tissues. There were distinct differences in tumor state ( P = 0.0417 ), pathological stage ( P = 0.0058 ), and T stage ( P = 0.0044 ). Comprehensive analysis of sequence and chip data also indicated that miR-1-3p was lowly expressed in HNSCC. The diagnostic performance of miR-1-3p in HNSCC is reflected in the sensitivity and specificity of the collection, etc. Bioinformatics analysis showed the possible biological process, cellular component, molecular function, and KEGG pathways of miR-1-3p in HNSCC. And ITGB4 was a possible target of miR-1-3p.Conclusions. miR-1-3p’s low expression may facilitate tumorigenesis and evolution in HNSCC through signaling pathways. ITGB4 may be a key gene in targeting pathways but still needs verification through in vitro experiments.

Comparison of the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging for oropharyngeal squamous cell carcinomas (OPSCC): A Surveillance, Epidemiology and End Results Program (SEER) database analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17538-e17538
Author(s):  
Sumita Trivedi ◽  
Haocan Song ◽  
Yuan Liu ◽  
Conor Ernst Steuer ◽  
William Stokes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Squamous Cell Carcinomas ◽  
Stage I ◽  
Seer Database ◽  
Free Survival ◽  
Ajcc Staging ◽  
Disease Free

e17538 Background: The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, incorporates significant changes to the prior seventh edition. The changes reflect the improved understanding of tumor biology, prognostic factors and molecular markers that effect outcomes in Head and Neck cancers. A key update restages OPSCC by human papilloma virus (HPV) positive and negative cancers as data demonstrated that these tumors have significantly different biology and outcomes. Methods: Using SEER data from 2004 – 2014, we identified male patients with squamous cell carcinomas of the tonsil, base of tongue and soft palate aged between 21 and 64 years old (those clinical characterizes were considered as surrogate markers for HPV positive status). We classified them by the AJCC 8th edition staging for HPV positive OPSCC and by AJCC 7th edition staging. The prediction performance by two staging editions were compared regarding overall survival (OS) and Disease free survival (DFS). Kaplan-Meier method and Cox proportional hazard model were applied, and the discrimination performance was measured by the concordance statistics (C-statistics). Results: A total of 8202 eligible patients were included in the analysis with a median follow up period of 51 months. 7415 (90.4%) patients had previously received radiation and 7038 (85.8%) patients had previously received chemotherapy. The median age of patients was 56 years. Distribution of stage I disease increased from 2% to 19.6% in AJCC 8th edition. 10-year overall survival (OS) for AJCC 8th stages I (74%), II (78%), III (55%) and IV (32%). Using Stage I as reference, the hazard ratio for stage II, III, and IV is 0.98 (95%CI: 0.87-1.09), 2.29 (95%CI: 2.04-2.57), and 5.88 (95%CI: 4.96-6.98). Similar results were noted for ten year disease free survival. The C-statistics measured overall discrimination for 8th edition is 0.68 and 0.63 for the 7th edition (P < 0.001). Conclusions: Based on this SEER analysis, the overall performance of discrimination improved from AJCC 7th to 8th edition; but in this study population, AJCC 8th edition does not distinguish stage I and II sufficiently as expected as it does for stages III and IV disease. Limitations of the SEER database include the surrogate for P16 status and under reported and incomplete data.

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