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https://www.readbyqxmd.com/read/28522603/smad4-loss-is-associated-with-cetuximab-resistance-and-induction-of-mapk-jnk-activation-in-head-and-neck-cancer-cells
#1
Hiroyuki Ozawa, Ruchira Ranaweera, Evgeny Izumchenko, Eugene Makarev, Alex Zhavoronkov, Elana J Fertig, Jason D Howard, Ana Markovic, Atul Bedi, Rajani Ravi, Jimena Perez, Quynh-Thu Le, Christina S Kong, Richard C K Jordan, Hao Wang, Hyunseok Kang, Harry Quon, David Sidransky, Christine H Chung
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. Experimental Design: SMAD4 expression was assessed by immunohistochemistry in 130 newly diagnosed and 43 recurrent HNSCC patients. Correlative statistical analysis with clinicopathological data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels...
May 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28490889/identification-of-potential-biomarkers-and-analysis-of-prognostic-values-in-head-and-neck-squamous-cell-carcinoma-by-bioinformatics-analysis
#2
Bo Yang, Zhifeng Chen, Yu Huang, Guoxu Han, Weizhong Li
The purpose of this study was to find disease-associated genes and potential mechanisms in head and neck squamous cell carcinoma (HNSCC) with deoxyribonucleic acid microarrays. The gene expression profiles of GSE6791 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were obtained with packages in R language and STRING constructed protein-protein interaction (PPI) network of the DEGs with combined score >0.8. Subsequently, module analysis of the PPI network was performed by Molecular Complex Detection plugin and functions and pathways of the hub gene in subnetwork were studied...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28474265/gene-expression-signatures-for-head-and-neck-cancer-patient-stratification-are-results-ready-for-clinical-application
#3
REVIEW
Luca Tonella, Marco Giannoccaro, Salvatore Alfieri, Silvana Canevari, Loris De Cecco
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide and considering the recent EUROCARE-5 population-based study the 5-year survival rate of HNSCC patients in Europe ranges between 69% in localized cases and 34% in patients with regional involvement. The development of high-throughput gene expression assays in the last two decades has provided the invaluable opportunity to improve our knowledge on cancer biology and to identify predictive signatures in the most deeply analyzed malignancies, such as hematological and breast cancers...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28405244/clusterization-in-head-and-neck-squamous-carcinomas-based-on-lncrna-expression-molecular-and-clinical-correlates
#4
Pelayo G de Lena, Abel Paz-Gallardo, Jesús M Paramio, Ramón García-Escudero
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer types such as head and neck squamous cell carcinomas (HNSCCs). RESULTS: Here, we use RNAseq expression data from The Cancer Genome Atlas (TCGA) and various statistic and software tools in order to get insight about the lncRNome in HNSCC...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28351564/role-of-cancer-stem-cell-marker-doublecortin-like-kinase-1-in-head-and-neck-squamous-cell-carcinoma
#5
Lorenz Kadletz, Dietmar Thurnher, Robert Wiebringhaus, Boban M Erovic, Ulana Kotowski, Sven Schneider, Rainer Schmid, Lukas Kenner, Gregor Heiduschka
BACKGROUND: So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro. METHODS: We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#6
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 2017: EBioMedicine
https://www.readbyqxmd.com/read/28255813/gene-promoter-associated-cpg-island-hypermethylation-in-squamous-cell-carcinoma-of-the-tongue
#7
Samatha Bhat, Shama Prasada Kabekkodu, Chinchu Jayaprakash, Raghu Radhakrishnan, Satadru Ray, Kapaettu Satyamoorthy
The present study was undertaken to explore and validate novel hypermethylated DNA regions in squamous cell carcinoma of the tongue (SCCT). Genome-wide methylation changes were identified by differential methylation hybridization (DMH) microarray and validated by bisulfite genome sequencing (BGS). The results were compared against datasets from The Cancer Genome Atlas head and neck squamous cell carcinoma (TCGA-HNSCC), Gene Expression Omnibus (GSE26549), and ArrayExpress (E-MTAB-1328). DMH identified 116 hypomethylated and 241 hypermethylated regions...
April 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28174608/genome-wide-dna-methylation-profile-identified-a-unique-set-of-differentially-methylated-immune-genes-in-oral-squamous-cell-carcinoma-patients-in-india
#8
Baidehi Basu, Joyeeta Chakraborty, Aditi Chandra, Atul Katarkar, Jadav Ritesh Kumar Baldevbhai, Debjit Dhar Chowdhury, Jay Gopal Ray, Keya Chaudhuri, Raghunath Chatterjee
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#9
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28146432/integrative-computational-analysis-of-transcriptional-and-epigenetic-alterations-implicates-dtx1-as-a-putative-tumor-suppressor-gene-in-hnscc
#10
Daria A Gaykalova, Veronika Zizkova, Theresa Guo, Ilse Tiscareno, Yingying Wei, Rajita Vatapalli, Patrick T Hennessey, Julie Ahn, Ludmila Danilova, Zubair Khan, Justin A Bishop, J Silvio Gutkind, Wayne M Koch, William H Westra, Elana J Fertig, Michael F Ochs, Joseph A Califano
Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146422/mage-expression-in-head-and-neck-squamous-cell-carcinoma-primary-tumors-lymph-node-metastases-and-respective-recurrences-implications-for-immunotherapy
#11
Simon Laban, Gregor Giebel, Niklas Klümper, Andreas Schröck, Johannes Doescher, Giulio Spagnoli, Julia Thierauf, Marie-Nicole Theodoraki, Romain Remark, Sacha Gnjatic, Rosemarie Krupar, Andrew G Sikora, Geert Litjens, Niels Grabe, Glen Kristiansen, Friedrich Bootz, Patrick J Schuler, Cornelia Brunner, Johannes Brägelmann, Thomas K Hoffmann, Sven Perner
Melanoma associated antigens (MAGE) are potential targets for immunotherapy and have been associated with poor overall survival (OS) in head and neck squamous cell carcinoma (HNSCC). However, little is known about MAGE in lymph node metastases (LNM) and recurrent disease (RD) of HNSCC.To assess whether MAGE expression increases with metastasis or recurrence, a tissue microarray (TMA) of 552 primary tumors (PT), 219 LNM and 75 RD was evaluated by immunohistochemistry for MAGE antigens using three monoclonal antibodies to multiple MAGE family members...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28109471/smoking-status-regulates-a-novel-panel-of-piwi-interacting-rnas-in-head-and-neck-squamous-cell-carcinoma
#12
Aswini R Krishnan, Avinaash Korrapati, Angela E Zou, Yuanhao Qu, Xiao Qi Wang, Joseph A Califano, Jessica Wang-Rodriguez, Scott M Lippman, Melbourne F Hovell, Weg M Ongkeko
OBJECTIVE: Smoking remains a primary etiological factor in head and neck squamous cell carcinoma (HNSCC). Given that non-coding RNAs (ncRNAs), including PIWI-interacting RNAs (piRNAs), have emerged as mediators of initiation and progression in head and neck malignancies, we undertook a global study of piRNA expression patterns in smoking-associated HNSCC. MATERIALS AND METHODS: Using RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atlas (TCGA), we analyzed the differential expression patterns of 27,127 piRNAs across patient cohorts stratified by tobacco use, with HPV16 status and tumor status taken into account...
February 2017: Oral Oncology
https://www.readbyqxmd.com/read/28039268/therapeutic-small-molecules-target-inhibitor-of-apoptosis-proteins-in-cancers-with-deregulation-of-extrinsic-and-intrinsic-cell-death-pathways
#13
REVIEW
Adeeb Derakhshan, Zhong Chen, Carter Van Waes
The Cancer Genome Atlas (TCGA) has unveiled genomic deregulation of various components of the extrinsic and intrinsic apoptotic pathways in different types of cancers. Such alterations are particularly common in head and neck squamous cell carcinomas (HNSCC), which frequently display amplification and overexpression of the Fas-associated via death domain (FADD) and inhibitor of apoptosis proteins (IAP) that complex with members of the TNF receptor family. Second mitochondria-derived activator of caspases (SMAC) mimetics, modeled after the endogenous IAP antagonist SMAC, and IAP inhibitors represent important classes of novel small molecules currently in phase I/II clinical trials...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#14
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27859938/head-and-neck-squamous-cell-carcinoma-ambiguous-human-papillomavirus-status-elevated-p16-and-deleted-retinoblastoma-1
#15
Tim N Beck, Chad H Smith, Douglas B Flieder, Thomas J Galloway, John A Ridge, Erica A Golemis, Ranee Mehra
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is potentially curable, but treatment planning remains a challenge. Oncogenic human papillomavirus (HPV)-positive disease is often associated with a good prognosis compared with HPV-negative disease. However, some HPV-positive HNSCC recurs, often with distant metastases and significant treatment resistance. METHODS AND RESULTS: We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high-risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5-17) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1)...
March 2017: Head & Neck
https://www.readbyqxmd.com/read/27855189/genomic-and-transcriptomic-alterations-associated-with-stat3-activation-in-head-and-neck-cancer
#16
Noah D Peyser, Kelsey Pendleton, William E Gooding, Vivian W Y Lui, Daniel E Johnson, Jennifer R Grandis
BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). METHODS AND FINDINGS: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression...
2016: PloS One
https://www.readbyqxmd.com/read/27777979/the-head-and-neck-cancer-immune-landscape-and-its-immunotherapeutic-implications
#17
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27669890/epidermal-growth-factor-egf-receptor-ligand-based-molecular-staging-predicts-prognosis-in-head-and-neck-squamous-cell-carcinoma-partly-due-to-deregulated-egf-induced-amphiregulin-expression
#18
Jian Gao, Camilla H Ulekleiv, Trond S Halstensen
BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients...
September 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27658780/hox-genes-potential-candidates-for-the-progression-of-laryngeal-squamous-cell-carcinoma
#19
Rafaela de Barros E Lima Bueno, Anelisa Ramão, Daniel Guariz Pinheiro, Cleidson Padua Alves, Vinicius Kannen, Achim A Jungbluth, Luiza Ferreira de Araújo, Bruna Rodrigues Muys, Aline Simoneti Fonseca, Jessica Rodrigues Plaça, Rodrigo Alexandre Panepucci, Luciano Neder, Fabiano P Saggioro, Rui Celso M Mamede, David Livingstone Alves Figueiredo, Wilson Araújo Silva
Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27650546/cogaps-matrix-factorization-algorithm-identifies-transcriptional-changes-in-ap-2alpha-target-genes-in-feedback-from-therapeutic-inhibition-of-the-egfr-network
#20
Elana J Fertig, Hiroyuki Ozawa, Manjusha Thakar, Jason D Howard, Luciane T Kagohara, Gabriel Krigsfeld, Ruchira S Ranaweera, Robert M Hughes, Jimena Perez, Siân Jones, Alexander V Favorov, Jacob Carey, Genevieve Stein-O'Brien, Daria A Gaykalova, Michael F Ochs, Christine H Chung
Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations. We modify the HaCaT keratinocyte cell line model to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background...
November 8, 2016: Oncotarget
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