Dataset Information

Increasing incidence and improving survival of oral tongue squamous cell carcinoma.

ABSTRACT: We evaluated changes in incidence, relative survival (RS), and conditional survival (CS) of head and neck squamous cell carcinoma (HNSCC), focusing on oral tongue squamous cell carcinoma (OTSCC). Data of 74 680 HNSCC patients from 1976 to 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Five anatomical sites and their subsites were analyzed. Annual percent change (APC) of incidence was calculated. RS and CS were compared across the four decades. Adjusted hazard ratios (aHRs) of RS were evaluated using multivariate regression. OTSCC incidence decreased from 1976 (APC = -0.76, P < 0.05) but has increased since 1999 (APC = 2.36, P < 0.05). During 2006-2015, the 5-year CS exceeded 90% only for OTSCC and oropharyngeal squamous cell carcinoma (OPSCC). RS improved in OTSCC (aHR = 0.697, 95% confidence interval [CI] 0.642-0.757, P < 0.001) and OPSCC (aHR = 0.669, 95% CI 0.633-0.706, P < 0.001) during the last two decades. For both OTSCC and OPSCC, improved survival was observed regardless of treatment. Incidence and survival remained unchanged for nasopharyngeal, hypopharyngeal, and laryngeal cancers during this period. In conclusion, OTSCC incidence has been increasing since the 2000s, with improving prognosis irrespective of treatment. Given its similarity to OPSCC, OTSCC may represent an emerging HNSCC, warranting further research and clinical recognition.

SUBMITTER: Kim YJ

PROVIDER: S-EPMC7217912 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Oral tongue squamous cell carcinoma (OTSCC) is one of the most common head and neck cancers. Innate or acquired resistance to cisplatin, a standard chemotherapy agent for OTSCC, is common in patients with OTSCC. Understanding the molecular basis for cisplatin chemoresistance in OTSCC cells may serve as a basis for identification of novel therapeutic targets. Podocalyxin (PODXL) has been found critical for malignant progression in a variety of cancers. Bmi1 has recently been found to induce cell apoptosis and cisplatin chemosensitivity in OTSCC cells. In this study, we explored the interaction between PODXL and Bmi1 in OTSCC cells, and assessed its impact on OTSCC cell chemoresistance to cisplatin. PODXL and/or Bmi1 were stably overexpressed or knocked down in SCC-4 and Tca8113 human OTSCC cells. Overexpression of PODXL in both cell lines markedly elevated the expression level of Bmi1 and the half maximal inhibitory concentration (IC50) of cisplain and reduced cisplatin-induced cell apoptosis, which was abolished by knockdown of Bmi1 or a selective focal adhesion kinase (FAK) inhibitor. On the other hand, knockdown of PODXL significantly decreased the Bmi1 expression level and cisplatin IC50 and increased cisplatin-induced cell apoptosis, which was completely reversed by overexpression of Bmi1. While overexpression and knockdown of PODXL respectively increased and decreased the FAK activity, Bmi1 showed no significant effect on the FAK activity in OTSCC cells. In addition, overexpression of PODXL markedly elevated the stability of Bmi1 mRNA, which was abolished by a selective FAK inhibitor. In conclusion, this study provides the first evidence that PODXL up-regulates the expression level of Bmi1 in OTSCC cells by increasing the stability of Bmi1 mRNA through a FAK-dependent mechanism; this effect leads to enhanced cisplatin chemoresistance in OTSCC cells. This study adds new insights into the molecular mechanisms underlying OTSCC chemoresistance.

Project description:BackgroundOral tongue squamous cell carcinoma (OTSCC) is a devastating tumor with poor prognosis. There is an urgent need for reliable biomarkers to help predict prognosis and guide treatment for OTSCC. In the current study, we aimed to develop a robust multi-gene signature and prognostic nomogram to predict the prognosis of patients with non-distant metastatic OTSCC.MethodsOTSCC-related differentially-expressed genes were screened from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression based on 1,000 bootstrap replicates, LASSO regression and stepwise multivariate Cox regression were utilized to develop a novel multi-mRNA signature for predicting overall survival in OTSCC. The concordance index, area under receiver operating characteristic (ROC AUC) and calibration curve were employed to assess the prediction capacity of the novel multi-gene model. In addition, a prognostic nomogram was constructed to facilitate the clinical use of the fitted model. The Kaplan-Meier with log-rank test was employed to assess differences in overall survival.ResultsWe successfully established a novel 15-mRNA prognostic model for predicting overall survival of non-distant metastatic OTSCC, involving ADTRP, ITGA3, RFC4, CCDC96, CYP2J2, NELL2, SPHK1, SPAG16, HBEGF, S100A9, EGFL6, ADGRG6, PDE4D, ABCA4, and CTTN. The prediction ability of this 15-gene signature was independent of other clinicopathological factors, with an HR of 11.5 (95% CI: 4.70-28.3). Moreover, internal validation by bootstrap analysis yielded a C-index of 0.849, with a 3-year AUC of 0.907 and 5-year AUC of 0.944, which implied excellent prediction accuracy of the fitted model. In addition, external validation by using the GEO dataset (GSE41116) yielded a C-index of 0.804, with a 3-year AUC of 0.868 and 5-year AUC of 0.855, which also indicated good prediction ability of the 15-gene model. Finally, a prognostic nomogram integrating risk group, grade, T stage and N stage was established.ConclusionOur results demonstrate our 15-gene signature was independently associated with overall survival in non-distant metastatic OTSCC. Moreover, the prognostic nomogram integrating the 15-gene signature and clinicopathological factors has potential to be developed as a prognostic tool.

Dataset Information

Increasing incidence and improving survival of oral tongue squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets