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A gene expression profiling to predict recurrence of advanced tongue squamous cell carcinoma (TSCC): Discovery and external validation

ABSTRACT: Though several approaches for improving therapy have been carried out, the prognoses of TSCC patients still remains poor. Furthermore, biological markers, which are able to distinguish patients at high risk of recurrence has not been sufficiently explored. In this study, we identified and validated the 30-specific genes for predicting TSCC patiens prognosis. In addition, the gene expression profiling data was successfully converted to protein expression profiling data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE78060 | GEO | 2017/07/31

SECONDARY ACCESSION(S): PRJNA312487

REPOSITORIES: GEO

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Whole Transcriptome sequencing TSCC (tongue squamous cell carcinoma)

Project description:Of the multiple anatomical sites represented in oral cancer, squamous cell carcinoma of the tongue (TSCC) shows the highest incidence among younger age group. Chewing betel leaf, areca nut & slaked lime and smoking tobacco are common practises in India which have direct clinical implication in TSCC carcinogenesis. Here, for the first time we define the landscape of genomic alterations in TSCC from the Indian diaspora which would help to identify novel therapeutic targets for clinical intervention and define the genetic basis for TSCC. We performed high throughput sequencing of fifty four tongue samples using whole exome sequencing (n=47, 23 paired normal tumor and 1 unpaired) and transcriptome sequencing (n=17, 10 tumor and 5 normal). Mutation, copy number analysis were carried out using exome sequencing data and transcriptome analysis provided expressed genes and transcript fusions in tongue cancer patients. Further, integrated analysis were performed to identify biologically relevant alterations. Our preliminary analysis revealed presence of most frequently altered mutations in TSCC which includes mutations in TP53, NOTCH1, CDKN2A, USP6, KMT2D etc, consistent with literature. We observed high frequency of CG/T(GC/A) transversions in non-CpG islands, a signature associated with tobacco exposure. Somatic copy number analysis revealed copy number gain in known hallmarks such as CCND1, MYC, ORAOV1 genes along with copy number alteration in novel genes. Significant positive correlation was observed in the genes harbouring copy number gains and showing increased expression.

2018-05-31 | E-MTAB-4654 | biostudies-arrayexpress

Gene expression profiling to predict recurrence of advanced squamous cell carcinoma of the tongue: discovery and external validation.

Project description:ObjectivesTo establish a prognostic signature for locally advanced tongue squamous cell carcinoma (TSCC) patients treated with surgery.ResultsIn the discovery study, unsupervised hierarchical clustering analysis identified two clusters which differentiated the Kaplan-Meier curves of RFS [median RFS, 111 days vs. not reached; log-rank test, P = 0.023]. The 30 genes identified were combined into a dichotomous PI. In the validation cohort, classification according to the PI was associated with RFS [median RFS, 754 days vs. not reached; log-rank test, P = 0.026 in GSE31056] and DSS [median DSS, 540 days vs. not reached; log-rank test, P = 0.046 in GSE42743 and 443 days vs. not reached; P < 0.001 in GSE41613]. Among genes, positive immunohistochemical staining of cytokeratin 4 was associated with favorable prognostic values for RFS (hazard ratio (HR), 0.591, P = 0.045) and DSS (HR, 0.333, P = 0.004).Materials and methodsWe conducted gene expression profiling of 26 clinicopathologically homogeneous advanced TSCC tissue samples using cDNA microarray as a discovery study. Candidate genes were screened using clustering analysis and univariate Cox regression analysis for relapse-free survival (RFS). These were combined into a prognostic index (PI), which was validated using three public microarray datasets of tongue and oral cancer (123 patients). Some genes identified in discovery were immunohistochemically examined for protein expression in another 127 TSCC patients.ConclusionWe identified robust molecular markers that showed significant associations with prognosis in TSCC patients. Gene expression profiling data were successfully converted to protein expression profiling data.

| S-EPMC5617464 | biostudies-literature

Whole exome sequencing of TSCC (tongue squamous cell carcinoma)

2018-05-31 | E-MTAB-4653 | biostudies-arrayexpress

LncRNA expression profiles in areca nut chewing induced Tongue Squamous Cell Carcinoma (TSCC) and matched paracancerous tissues

Project description:Chewing betel nut is an important risk factor for the carcinogenesis of tongue squamous cell carcinoma (TSCC), but the mechanism is still unknown.To screen the lncRNAs associated with betel nut chewing-induced TSCC and identify potential biomarkers for the TSCC, we collected 5 pairs of TSCC and paracancerous tissues and monitored the resultant lncRNA and mRNA expression profiles using an lncRNA microarray. All 5 patients have a history of areca nut chewing.

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Expression analysis of LncRNA in Tongue Squamous Cell Carcinoma (TSCC) and matched nonmalignant tissues (NC)

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2013-10-30 | E-GEOD-51700 | biostudies-arrayexpress

Altered expression of microRNAs in Tongue squamous cell carcinoma (TSCC) and matched nonmalignant tissues (NC)

Project description:Investigation of microRNA expression level changes in 4 paired of Tongue Squamous Cell Carcinoma specimens miRNA profiling: TSCC vs NC

2013-10-30 | E-GEOD-51829 | biostudies-arrayexpress

Whole Transcriptome sequencing TSCC (tongue squamous cell carcinoma)

Project description:Whole Transcriptome sequencing TSCC (tongue squamous cell carcinoma)

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Whole exome sequencing of TSCC (tongue squamous cell carcinoma)

Project description:Whole exome sequencing of TSCC (tongue squamous cell carcinoma)

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Project description:MicroRNAs play a crucial role in tumorigenesis. However, the value of microRNAs in the diagnosis and treatment of tongue squamous cell carcinoma (TSCC) still await investigations. To identify the microRNAs associated with the metastasis of TSCC, we analyzed the transcriptomic difference between metastatic and the non-metastatic TSCC tissue. We identified a set of metastasis-related microRNAs with potential prognostic value.

2016-12-31 | GSE81821 | GEO

MicroRNA Expression Profiling of Saliva in Tongue Squamous Cell Carcinoma Patients

Project description:41% of all oral carcinomas have been found to localize at tongue, where they were characterized as being aggressive and having capacity to locally invade and relapse frequently. Despite considerable enhancements in the cancer diagnosis and treatment techniques, tongue squamous cell carcinoma (TSCC) still remains to be one of the most common and lethal cancer types in the head and neck region. In this study, we aimed to identify a signature of saliva-specific microRNAs (miRNAs) expression in TSCC patients. To explore putative diagnostic biomarkers, we compared the miRNA profiles of saliva samples obtained from 3 TSCC patients and 4 healthy control individual using Agilent miRNA microarray (V19). Three of the differentially expressed miRNAs were selected for further validation with quantitative reverse-transcription PCR (qRT-PCR) using saliva samples of 25 TSCC patients and 25 healthy control individuals. Microarray analysis demonstrated that 428 miRNA probes were deregulated in TSCC patients when compared to control group and qRT-PCR results validated the reduced expression of miR-139-5p in TSCC saliva. Further analysis of post-operative saliva samples of TSCC patients revealed that miR-139-5p level elevated to normal level after surgery, pointing its diagnostic and prognostic power. As a conclusion, we propose saliva as a feasible source in routine patient examination for early diagnosis of TSCC patients, and our results suggest saliva miR-139-5p as a novel potential diagnostic marker.

2016-10-20 | GSE69002 | GEO

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