Dataset Information

A 3-mRNA-based prognostic signature of survival in oral squamous cell carcinoma.

ABSTRACT: Background:Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma with an unsatisfactory prognosis. The aim of this study was to identify potential prognostic mRNA biomarkers of OSCC based on analysis of The Cancer Genome Atlas (TCGA). Methods:Expression profiles and clinical data of OSCC patients were collected from TCGA database. Univariate Cox analysis and the least absolute shrinkage and selection operator Cox (LASSO Cox) regression were used to primarily screen prognostic biomarkers. Then multivariate Cox analysis was performed to build a prognostic model based on the selected prognostic mRNAs. Nomograms were generated to predict the individual's overall survival at 3 and 5 years. The model performance was assessed by the time-dependent receiver operating characteristic (ROC) curve and calibration plot in both training cohort and validation cohort (GSE41613 from NCBI GEO databases). In addition, machine learning was used to assess the importance of risk factors of OSCC. Finally, in order to explore the potential mechanisms of OSCC, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was completed. Results:Three mRNAs (CLEC3B, C6 and CLCN1) were finally identified as a prognostic biomarker pattern. The risk score was imputed as: (-0.38602 × expression level of CLEC3B) + (-0.20632 × expression level of CLCN1) + (0.31541 × expression level of C6). In the TCGA training cohort, the area under the curve (AUC) was 0.705 and 0.711 for 3- and 5-year survival, respectively. In the validation cohort, AUC was 0.718 and 0.717 for 3- and 5-year survival. A satisfactory agreement between predictive values and observation values was demonstrated by the calibration curve in the probabilities of 3- and 5- year survival in both cohorts. Furthermore, machine learning identified the 3-mRNA signature as the most important risk factor to survival of OSCC. Neuroactive ligand-receptor interaction was most enriched mostly in KEGG pathway analysis. Conclusion:A 3-mRNA signature (CLEC3B, C6 and CLCN1) successfully predicted the survival of OSCC patients in both training and test cohort. In addition, this signature was an independent and the most important risk factor of OSCC.

SUBMITTER: Cao R

PROVIDER: S-EPMC6679650 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A 3-mRNA-based prognostic signature of survival in oral squamous cell carcinoma.

Cao Ruoyan R Wu Qiqi Q Li Qiulan Q Yao Mianfeng M Zhou Hongbo H

PeerJ 20190731

<h4>Background</h4>Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma with an unsatisfactory prognosis. The aim of this study was to identify potential prognostic mRNA biomarkers of OSCC based on analysis of The Cancer Genome Atlas (TCGA).<h4>Methods</h4>Expression profiles and clinical data of OSCC patients were collected from TCGA database. Univariate Cox analysis and the least absolute shrinkage and selection operator Cox (LASSO Cox) regressio ...[more]

PMID: 31396442

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Project description:Objectives: This study was designed to identify a messenger RNA (mRNA) expression signature to predict survival in patients with oral squamous cell carcinoma (OSCC). Methods: mRNA expression profiles were integrated with clinical data from 280 samples, including 19 normal tissues and 261 OSCC tissues in The Cancer Genome Atlas. We identified differentially expressed mRNAs (DEmRNAs) between the OSCC and normal tissue samples and developed a novel mRNA-focused expression signature using a Cox regression analysis and other bioinformatic methods. The prognostic value of this signature was evaluated by Kaplan-Meier analysis, multivariable COX regression, and receiver operating characteristic (ROC) curve analysis. Protein-protein interaction (PPI) network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to predict the function of the DEmRNAs. Signature-related mRNAs were analyzed by gene set enrichment analyses (GSEA) and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 20 paired OSCC and adjacent healthy tissues. Results: We identified a novel 5-mRNA expression signature (HOXA1, CELSR3, HIST1H3J, ZFP42, and ASCL4) that could predict patient outcomes in OSCC. The risk score based on the signature was able to separate OSCC patients into high- and low-risk groups that showed significantly different overall survival (p < 0.001, log-rank test). The signature was further validated as an effective independent prognostic predictor of OSCC by multivariate Cox regression analysis (hazard ratio = 3.747, confidence interval: 2.279-5.677, p < 0.001) and ROC curve of the third year (area under the curve = 0.733). Functional analysis demonstrated that the key hub genes in the PPI network were mainly enriched in cell division, cell proliferation, and the p53 signaling pathway. GSEA results showed that the 5 mRNAs were significantly enriched in mismatch repair, DNA replication, and the NOTCH signaling pathway. Finally, qRT-PCR results showed that the 5 mRNAs were upregulated in OSCC tissue in agreement with the predictions from our bioinformatics analysis. Conclusions: We identified a novel 5-mRNA signature that could predict the survival of patients with OSCC and may be a promising biomarker for personalized cancer treatments.

Project description:Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancy in the respiratory tract and could reduce the quality of life seriously like dyspnea, dysphonia and dysphagia. Moreover, 5-year survival rate has decreased over the past 40 years. This study was designed to identify mRNAs that related to prognosis in LSCC to enable early detection and outcome improvement. Methods: Gene expression profiles from Gene Expression Omnibus (GEO) (GSE59102, GSE84957) and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) with the help of bioinformatics tools. Functional enrichment analyses including Gene Ontology (GO) and pathway analysis were carried out to investigate the role of those genes and underlying molecular mechanisms in LSCC. Cox's regression analyses (univariate, LASSO and multivariate in order) were utilized to identify DEGs related with patients' overall survival and a 4-mRNA-based prognostic risk score model was established. Univariate and multivariate Cox's regression analyses were then performed on LSCC data (90 patients left) to identify independent predictors of OS, including the signature and clinicopathologic variables. The prognostic value of the gene signature was further validated and the genes were analyzed by GEPIA to get pan-cancer expression profiles. Results: 444 differentially expressed mRNAs (250 up-regulated, 194 down-regulated) were identified based on the threshold of fold change > 2 and adjusted p value < 0.05. Univariate Cox's regression analysis showed that high risk score (HR: 3.056, 95% confidence interval [CI]: 0.135-0.649, p<0.001) and female (HR: 0.296, 95% CI: 2.020-4.624, p=0.002) were associated with relatively poor prognosis. Further multivariate Cox's regression analysis indicated that risk score and gender were independent prognostic factors (p<0.05). The risk score model could stratify patients into high- and low‑risk groups, which presents significantly differential overall survival (p= 8.252e-04). The AUCs of 1-, 3- and 5-year OS were 0.724, 0.783 and 0.818, respectively. Conclusions: Our study provides evidence that the four-mRNA signature could serve as a biomarker to predict prognosis in LSCC, especially in long-term.

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

A 3-mRNA-based prognostic signature of survival in oral squamous cell carcinoma.

Publications

A 3-mRNA-based prognostic signature of survival in oral squamous cell carcinoma.

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