A 15-Gene Signature and Prognostic Nomogram for Predicting Overall Survival in Non-Distant Metastatic Oral Tongue Squamous Cell Carcinoma

Abstract

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.

FKBP1A upregulation correlates with poor prognosis and increased metastatic potential of HNSCC

“…Higher tumor stage (T‐stage) is a poor prognostic indicator of HNSCC (Li et al, 2021; M. Liu et al, 2021). To evaluate the clinical relevance of ATG12, HSP90AB1, and FKBP1A with the tumor stage, we analyzed in silico database GEO dataset containing HNSCC tissues of different tumor stages.…”

“…Higher tumor stage (T-stage) is a poor prognostic indicator of HNSCC (Li et al, 2021;M. Liu et al, 2021).…”

Salivary Metabolomics for Prognosis of Oral Squamous Cell Carcinoma

“…However, the liquid biopsy applied to blood, rather than saliva, as the biofluid ( 2 , 22 , 23 ). Most surveys were performed using genomics, transcriptomics, or proteomics approaches, rather than a metabolomics approach ( 2 , 24 , 25 ). To our knowledge, this is the first study to identify salivary metabolites for predicting the prognosis of OSCC, which makes our findings significant.…”

A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma

“…For instance, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, such public databases are desirable to access transcriptomic information, that advances the efficient methods to select gene signatures ( 26 – 28 ). Numerous studies have attempted to construct the risk model to get biological characteristics or prognostic appraisal in malignant tumors, which had potential clinical impact ( 29 – 31 ). Interestingly, EMT-related gene signature (E-signature) could reveal the prognostic consequences in various types of cancer ( 32 – 34 ).…”