Oral cavity and oropharyngeal squamous cell carcinoma genomics.
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ABSTRACT:
SUBMITTER: Tan M
PROVIDER: S-EPMC3734385 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
Oral cavity and oropharyngeal squamous cell carcinoma genomics.
Tan Marietta M Myers Jeffrey N JN Agrawal Nishant N
Otolaryngologic clinics of North America 20130617 4
Recent technological advances now permit the study of the entire cancer genome, which can elucidate complex pathway interactions that are not apparent at the level of single genes. In this review, the authors describe innovations that have allowed for whole-exome/genome analysis of genetic and epigenetic alterations and of changes in gene expression. Studies using next-generation sequencing, array comparative genomic hybridization, methylation arrays, and gene expression profiling are reviewed, ...[more]
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Project description:ObjectiveEvaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC).Study designRetrospective case series and subsequent prospective cohort study SETTING: Tertiary care academic teaching hospital SUBJECTS AND METHODS: Retrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 - December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 - December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost.ResultsAnalysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD.ConclusionImplementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.
| S-EPMC8218466 | biostudies-literature
Project description:IntroductionFibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort.MethodsProtein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation.ResultsFGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p > 0.05).ConclusionFGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients.
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Project description:Background:Oral squamous cell carcinoma (SCC) is the most common oral malignancy. Some evidence indicated that there is a correlation between microRNA single nucleotide polymorphisms and the risk of oral cancer. The aim of the current study was to investigate the association between mir-499 polymorphism with the risk of oral cavity and oropharyngeal SCC in a subset of Iranian Population. Materials and Methods:In this case-control pilot study total of 112 participants including 56 histopathlogically confirmed oral and oropharyngeal SCC patients and 56 age- and sex-matched controls were included The mir-499 rs3746444 T/C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism method. The comparisons of the distribution of the allele and genotype frequencies were performed using Chi-square test, and P < 0.05 was considered as statistically significant. Results:The result of the present study indicated that the frequency distribution of mir-499 was not significantly different between cases and controls (P > 0.05). We also did not find any significant association between the risk of the cancer and mir-499 polymorphisms in the recessive (Odds ratio [OR]: 6.60; 95% confidence interval [CI]: 0.77-56.74; P = 0.11) and dominant (OR: 1; 95% CI: 0.37-2.74; P = 1) inheritance models even after adjustment for smoking. Conclusion:The results of the present study indicated that the polymorphisms of mir-499 are not associated with the risk of oral and oropharyngeal SCC in Iranian population. However, further large scale studies are needed to validate our findings.
| S-EPMC7386373 | biostudies-literature
Project description:The incidence of oral squamous cell carcinoma (OSCC) continues to increase each year. Clinical examination and biopsy usually detect OSCC at an advanced stage that is difficult to treat, leading to poor prognosis. DNA methylation pattern is tissue specific and has emerged as a biomarker for the detection of cancers of tissue origin. Herein, we aimed to discover a novel site-specific methylation marker for OSCC.We selected OSCC datasets analyzed using the IlluminaHumanMethylation27 BeadChip from the Gene Expression Omnibus repository of the National Center for Biotechnology Information using a bioinformatics approach. From 27,578 CG dinucleotide (CpG) sites, the CpG site with the highest difference in methylation level between healthy and cancerous cells was selected for further validation. A total of 18 mucosal tissue samples were collected from nine healthy controls and nine from OSCC subjects and subjected to microdissection for cell purification, followed by DNA extraction, bisulfite conversion, and pyrosequencing. Additionally, epithelial cells were collected from 2 cohorts including oral rinse from healthy controls, oral rinse and oral swab from OSCC subjects and oral rinse from oropharyngeal squamous cell carcinoma (SCC) were examined for their methylation status using real-time polymerase chain reaction (PCR).Among the 27,578 differentially methylated CpG sites, cg01009664 of the thyrotropin-releasing hormone (TRH) gene showed the greatest difference in methylation level between healthy and cancerous cells. Validation of the TRH gene using pyrosequencing revealed a methylation percentage of 7%?±?3.43% in healthy cells in contrast to 63%?±?19.81% in cancerous cells. Screening of epithelial cells using real-time PCR showed that the DNA methylation level was significantly higher in oral swab and rinse samples collected from OSCC and oropharyngeal SCC subjects than those from healthy controls (p?<?0.001). In addition, when using a cutoff at 3.31 ng/?L, the TRH methylation biomarker was able to distinguish OSCC and oropharyngeal SCC subjects from healthy controls with high level of area under the curve, sensitivity and specificity.We demonstrated cg01009664 of TRH as a potential biomarker for OSCC and oropharyngeal SCC screening using oral rinse and swab techniques.
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Project description:ASC (Apoptosis-associated Speck-like protein containing a CARD) acts as a platform protein in the inflammasome cascade of some cancer types. However, its potential involvement in OSCC (oral cavity squamous cell carcinoma) has not yet been determined. Here, we investigated the potential role of ASC in OSCC. RT-qPCR analysis of 20 paired tumor and adjacent normal tissue samples revealed that the mRNA levels of ASC, along with IL-1?, CASP1, and NLRP3 in ASC-associated NLRP3 inflammasome were significantly elevated in OSCC tissues. Immunohistochemical staining of these four proteins in 111 clinical specimens revealed that high-level expression of ASC was significantly associated with tumor stage, node stage (p=0.001), overall stage (p<0.001), extracapsular spread (p<0.001), perineural invasion (p=0.004) and tumor depth (p<0.001). Kaplan-Meier survival analysis further revealed that high-level ASC expression was correlated with poorer overall survival (p=0.001), disease-specific survival (p<0.001) and disease-free survival (p<0.001). Studies using OSCC cell lines indicated that high-level ASC expression enhanced cell migration and invasion, and experiments using an orthotropic nude mouse model confirmed that ASC overexpression induced metastasis of OSCC cells. This is the first report to show that ASC contributes to OSCC metastasis, and that high-level ASC expression is a marker for poor prognosis in OSCC patients.
| S-EPMC5226569 | biostudies-literature
Project description:Cancer stem cells (CSCs) have been identified in oral cavity squamous cell carcinoma (OCSCC). CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including OCSCC have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OCSCC, making investigation reliant on the use of multiple markers. This review examines the current knowledge in CSC markers OCT4, SOX2, NANOG, ALDH1, phosphorylated STAT3, CD44, CD24, CD133, and Musashi-1, specifically focusing on their use and validity in OCSCC CSC research and how they may be organized into the CSC hierarchy. OCSCC CSCs also express components of the renin-angiotensin system (RAS), which suggests CSCs may be novel therapeutic targets by modulation of the RAS using existing medications.
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Project description:Summary Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon’s two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%–53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993). Graphical abstract Highlights • Presurgical nivolumab in patients with resectable oral cancer has an ORR of 33%• 10 out of 12 treated patients remain alive with a median follow up of 2.23 years• Neoadjuvant nivolumab is safe, well-tolerated, and not associated with treatment delays• This shows feasibility of nivolumab in the neoadjuvant setting for OCSCC (NCT03021993) Oral cavity squamous cell carcinoma is a prevalent subset of head and neck cancer with high recurrence rates and poor survival outcomes despite complex multimodality therapy. The current study by Knochelmann et al. demonstrates that presurgical nivolumab therapy has an overall response rate of 33% in this patient population.
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Project description:Gene expression profiling of 66 HPV-negative OSCC primary tumor was performed to identify gene expression that is related to lymph node metastasis and poor prognosis. These gene expression profiles were combined in silico with gene expression profiles of 84 OSCC primary tumors retrieved from GSE30788.
2017-08-10 | GSE85446 | GEO
Project description:Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.
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Project description:OBJECTIVES:We sought to describe the genetic complexity of 14 UM-SCC oral cavity cancer cell lines that have remained uncharacterized despite being used as model systems for decades. MATERIALS AND METHODS:We performed exome sequencing on 14 oral cavity UM-SCC cell lines and denote the mutational profile of each line. We used a SNP array to profile the multiple copy number variations of each cell line and use immunoblotting to compare alterations to protein expression of commonly amplified genes (EGFR, PIK3CA, etc.). RNA sequencing was performed to characterize the expression of genes with copy number alterations. RESULTS:The cell lines displayed a highly complex network of genetic aberrations that was consistent with alterations identified in the HNSCC TCGA project including PIK3CA amplification, CDKN2A deletion, as well as TP53 and CASP8 mutations, enabling genetic stratification of each cell line in the panel. Copy number FISH and spectral karyotyping analysis demonstrate that cell lines retain chromosomal heterogeneity. CONCLUSIONS:Collectively, we developed an important resource for future oral cavity HNSCC cell line studies and highlight the complexity of genomic aberrations in cell lines.
| S-EPMC6349383 | biostudies-literature