Východiska: Spinocelulární karcinom dutiny ústní (oral squamous cell carcinoma – OSCC) je nejběžnějším typem zhoubných nádorů v oblasti hlavy a krku. Je známo, že cirkulární RNA (circRNA) hraje důležitou roli v karcinogenezi různých typů zhoubných nádorů. Role circRNA při OSCC však zůstává nejasná. Materiál a metody: Byly získány tkáně OSCC a přilehlé normální tkáně k detekci exprese circRNA sekvenováním nové generace (next generation sequencing – NGS) a byly vybrány tkáně OSCC k ověření circRNAs různého významu pomocí kvantitativní polymerázové řetězové reakce s reverzní transkriptázou (reverse transcriptase-quantitative polymerase chain reaction – RT-qPCR). Pro další zkoumání role hsa-circ-0006203 – hsa-circ-0004872 byl vytvořen design primeru a byla provedena RT-PCR. Hladiny exprese byly detekovány pomocí RT-qPCR. Výsledky: Výsledky NGS ukázaly, že u OSCC byly výrazně exprimovány circRNA, přičemž dvě circRNAs byly exprimovány výrazně odlišným způsobem. hsa-circ-0006203 – hsa-circ-0004872 byly ve vzorcích tkáně OSCC výrazně downregulována, což statisticky korelovalo s jejich patologickou diferenciací. Závěr: Souhrnně lze říci, že výsledky prezentované studie odhalily zvýšené množství circRNA ve tkáních OSCC a pokud je nám známo, náš tým jako první zkoumal regulační roli sítě hsa-circ-0006203 – hsa-circ-0004872 u OSCC. Výsledky ukázaly, že hsa-circ-0006203 – hsa-circ-0004872 může být případným biomarkerem OSCC.

Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. Material and methods: OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by the next generation sequencing (NGS), and OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa-circ-0006203 – hsa-circ-0004872, the primer design and RT-PCR were performed. The expression levels were detected by RT-qPCR. Results: The NGS results demonstrated that circRNAs were abundantly expressed in OSCC, and two circRNAs were significantly differentially expressed. hsa-circ-0006203 – hsa-circ-0004872 were significantly downregulated in OSCC tissue samples and was statistically correlated with pathological differentiation. Conclusion: In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, it was our team who firstly explore the regulatory role of the hsa-circ-0006203 – hsa-circ-0004872 network in OSCC. The results indicated that hsa-circ-0006203 – hsa-circ-0004872 may be a potential biomarker for OSCC.

• Klíčová slova
• hsa-circ-0006203, hsa-circ-0004872,
• MeSH
• klinická studie jako téma MeSH
• kruhová RNA MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory úst * diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. METHODS: The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. RESULTS: A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. CONCLUSIONS: The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.

• MeSH
• adrenalin MeSH
• aurora kinasa A genetika   metabolismus   MeSH
• dlaždicobuněčné karcinomy hlavy a krku * genetika   MeSH
• genové regulační sítě MeSH
• kvalita života MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• mikro RNA * genetika   MeSH
• nádory úst * genetika   MeSH
• PPAR gama genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory genetika   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

• MeSH
• celogenomová asociační studie MeSH
• exprese genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• HLA antigeny klasifikace   genetika   imunologie   MeSH
• humorální imunita * MeSH
• infekce papilomavirem genetika   imunologie   patologie   virologie   MeSH
• kouření patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   patogenita   MeSH
• lokus kvantitativního znaku MeSH
• metaanalýza jako téma MeSH
• nádory orofaryngu genetika   imunologie   patologie   virologie   MeSH
• nádory úst genetika   imunologie   patologie   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• protilátky virové biosyntéza   MeSH
• represorové proteiny genetika   imunologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• virové plášťové proteiny genetika   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVES: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. MATERIALS AND METHODS: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. RESULTS: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. CONCLUSIONS: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• fixace tkání MeSH
• inhibitor p16 cyklin-dependentní kinasy metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 izolace a purifikace   MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   MeSH
• nádory úst genetika   metabolismus   patologie   MeSH
• plocha pod křivkou MeSH
• sekvenční analýza RNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom genetika   metabolismus   patologie   MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese metody   MeSH
• zalévání tkání do parafínu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

• MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• genetická variace genetika   MeSH
• genetické markery genetika   MeSH
• haplotypy genetika   MeSH
• HLA antigeny MeSH
• infekce papilomavirem genetika   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hltanu genetika   virologie   MeSH
• nádory úst genetika   virologie   MeSH
• Papillomaviridae izolace a purifikace   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• ústa metabolismus   patologie   virologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: Environmental and patho-physiologic stresses stimulate synthesis of heat shock proteins (HSPs) which enable the cell to survive and recover from stressful conditions, by as yet incompletely understood mechanisms. Heat shock proteins show an increased expression in a wide range of human cancers and have been associated with tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. Yet the role of heat shock proteins in oral cancer is ambiguous. The objective of this review was to systematically assess the data available on the role of HSP expression in oral cancer with special reference to its role in diagnosis, prognosis and treatment. METHODS AND RESULTS: A systematic review of studies that investigated the HSP expression in oral squamous cell carcinoma using Scopus, Medline, Embase and Google scholar databases from their inceptions to 2013, without language restrictions was conducted. We selected 24 studies from which data extraction and validations were performed. CONCLUSION: The literature search revealed differential expression of HSPs during oral tumorigenesis with implications for the specific role of HSPs in the pathogenesis of oral cancer. HSP expression has been regarded as an independent prognostic factor for oral squamous cell carcinoma patients and HSPs are being explored as potent vehicles for delivery of preventive and treatment vaccines in cancer and other diseases.

• MeSH
• DNA nádorová genetika   MeSH
• lidé MeSH
• molekulární chaperony MeSH
• nádory úst genetika   metabolismus   MeSH
• proteiny tepelného šoku biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• spinocelulární karcinom genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIMS: Cancer patient's inherited genotype may influence his or her survival, but evidence for the role of these genetic differences in oral cancer survival has not yet been explored. METHODS: The authors evaluated polymorphisms in the GSTM1 and CYP1A1 genes for associations with overall survival in 100 oral squamous cell carcinoma (OSCC) treated patients and 100 controls who were followed up for survival within 2 years of the date of completion of their treatment. Overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. RESULTS: After adjustment for stage and histology, GSTM1null genotype was associated with shorter survival among OSCC patients, compared with GSTM1 present genotype. There was no association between CYP1A1 C genotype and survival in the overall study population. CONCLUSION: The study indicated a potential role for GSTM1 polymorphism in predicting the clinical outcomes of treated oral carcinoma patients.

• MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• dospělí MeSH
• glutathiontransferasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory úst genetika   mortalita   MeSH
• polymorfismus genetický * MeSH
• senioři MeSH
• spinocelulární karcinom genetika   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Polymorphisms in the genes that code for metabolic enzymes involved in either the activation (Phase I) or detoxication (Phase II) of chemical carcinogens in tobacco, may alter expression or function of carcinogenic compounds and hence alter risk of oral cancer. The present study investigates whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral precancerous lesions and cancer. METHODS: For the present study, histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase chain reaction and restriction fragment length polymorphism were performed using DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1 loci. RESULTS: CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant association but the frequency was higher in oral SCC cases. Patients with genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco consumption than those of other genotypes though the difference was not statistically significant. The frequency of the combined genotypes C and GSTM1 null was found to be 14% among oral SCC patients. On comparing the susceptibility of intraoral sites it was found that in the majority of cases (64%) in the study groups they were the buccal mucosa. CONCLUSION: Hence it was concluded that metabolic enzymes reported in the present study: CYP1A1 significantly alter oral cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant lesions and cancer of the buccal mucosa than other sites.

• MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• glutathiontransferasa genetika   MeSH
• karcinogeny metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory úst genetika   MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický * MeSH
• prekancerózy genetika   MeSH
• rizikové faktory MeSH
• spinocelulární karcinom genetika   MeSH
• tabák enzymologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The microenvironment established by stromal cells may or may not influence phenotypic aspects of epithelial cells and may be relevant for tumor and stem cell biology. We address this issue for keratinocytes using tumor-derived stromal cells in a co-culture system. MATERIALS AND METHODS: We isolated stromal cells from human squamous cell carcinoma tissue and studied their effect on phenotypic characteristics of normal human interfollicular keratinocytes in vitro. RESULTS: Stromal fibroblasts significantly influence immuno- and lectin cytochemical properties of co-cultured normal keratinocytes. Expression of keratins 8 and 19, the nucleolar protein nucleostemin, parameters related to adhesion/growth-regulatory galectins and the epithelial-mesenchymal transition were altered. This biological activity of tumor-derived stromal cells, which did not require cell contact, appeared to be stable, because it was maintained during passaging of keratinocytes in the absence of cancer cells. CONCLUSIONS: Tumor-derived stromal fibroblasts acquire distinct properties to shape a microenvironment conducive to altering the phenotypic characteristics of normal epithelial cells in vitro.

• MeSH
• biologické markery metabolismus   MeSH
• buňky stromatu metabolismus   patologie   MeSH
• DNA primery genetika   MeSH
• fenotyp MeSH
• financování organizované MeSH
• genetické markery MeSH
• keratinocyty cytologie   metabolismus   MeSH
• keratiny metabolismus   MeSH
• kokultivační techniky MeSH
• lidé MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• nádory úst genetika   metabolismus   patologie   MeSH
• spinocelulární karcinom genetika   metabolismus   patologie   MeSH
• transplantace heterologní MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

• MeSH
• chromozomální aberace MeSH
• cytogenetika MeSH
• lidé MeSH
• nádory úst genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH