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Hnscc genomics

Ludmila Wintergerst, Martin Selmansberger, Cornelius Maihoefer, Lars Schüttrumpf, Axel Walch, Christina Wilke, Adriana Pitea, Christine Woischke, Philipp Baumeister, Thomas Kirchner, Claus Belka, Ute Ganswindt, Horst Zitzelsberger, Kristian Unger, Julia Hess
Previously, we have shown that copy number gain of the chromosomal band 16q24.3 is associated with impaired clinical outcome of radiotherapy-treated head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify a prognostic mRNA signature from genes located on 16q24.3 in radio(chemo)therapy-treated HNSCC patients of the TCGA (The Cancer Genome Atlas, n=99) cohort. We applied stepwise forward-selection using expression data of 41 16q24.3 genes. The resulting optimal Cox-proportional hazards regression model included the genes APRT, CENPBD1, CHMP1A and GALNS...
September 26, 2018: Molecular Oncology
Wei-Ning Cen, Jin-Shu Pang, Jia-Cheng Huang, Jia-Yin Hou, Wen-Guang Bao, Rong-Quan He, Jie Ma, Zhi-Gang Peng, Xiao-Hua Hu, Fu-Chao Ma
BACKGROUND: The specific expression level and clinical significance of miR-375-3p in HNSCC had not been fully stated, as well as the overall biological function and molecular mechanisms. Therefore, we purpose to carry out a comprehensive meta-analysis to further explore the clinical significance and potential function mechanism of miR-375-3p in HNSCC. METHODS: HNSCC-related data was gained from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and peer-reviewed journals...
September 13, 2018: Pathology, Research and Practice
Amber M Bates, Maria Paula Gomez Hernandez, Emily A Lanzel, Fang Qian, Kim A Brogden
Background: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally...
June 2018: Translational Cancer Research
Timo J Vogt, Heidrun Gevensleben, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Jennifer Landsberg, Diane Goltz, Dimo Dietrich
Background : The adenosine A2a receptor (A2aR) and the adenosine synthesizing enzyme CD73 have recently evolved as a novel immunotherapeutic target. However, little is known about epigenetic modification of the encoding genes ADORA2A and NT5E . Methods : In the present study, we evaluated methylation at 23 loci of ADORA2A and 17 loci of NT5E with regard to transcriptional activity, human papilloma virus (HPV) status, immune cell infiltration, and outcome in a cohort of 279 head and neck squamous carcinoma (HNSCC) patients obtained from The Cancer Genome Atlas (TCGA)...
2018: Oncoimmunology
Dong Jin Lee, Young-Gyu Eun, Young Soo Rho, Eui Hyun Kim, Sun Young Yim, Sang Hee Kang, Bo Hwa Sohn, Gee Hwan Kwon, Ju-Seog Lee
OBJECTIVES: Heterogeneity of head and neck squamous cell carcinomas (HNSCCs) results in unpredictable outcomes for patients with similar stages of cancer. Beyond the role of human papilloma virus (HPV), no validated molecular marker of HNSCCs has been established. Thus, clinically relevant molecular subtypes are needed to optimize HNSCC therapy. The purpose of this study was to identify subtypes of HNSCC that have distinct biological characteristics associated with clinical outcomes and to characterize genomic alterations that best reflect the biological and clinical characteristics of each subtype...
October 2018: Oral Oncology
Jixi Li, Kang Liu, Tingting Zhang, Zhendong Yang, Rensheng Wang, Gang Chen, Min Kang
HNSCC is the sixth most common cancer worldwide and is characterized as an aggressive, malignant tumor. MiR-34a-5p (miR-34a) expression has been strongly linked to HNSCC development. However, the exact target gene of miRNA-34a-as well as its biological and mechanistic pathways-are unclear. It is critical that the clinical value of HNSCC receive further study. We conducted a continuous variable, meta-analysis from data found in the cancer literature as well as that provided by the Cancer Genome Atlas (TCGA) to estimate miR-34a expression in HNSCC...
2018: American Journal of Translational Research
Yu-Zhu Guo, Hui-Hui Sun, Xiang-Ting Wang, Mei-Ting Wang
OBJECTIVE: In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. METHODS: RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA), including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated lncRNAs...
2018: Journal of Zhejiang University. Science. B
Stephen Mf Jamieson, Peter Tsai, Maria K Kondratyev, Pratha Budhani, Arthur Liu, Neil N Senzer, E Gabriela Chiorean, Shadia I Jalal, John J Nemunaitis, Dennis Kee, Avik Shome, Way W Wong, Dan Li, Nooriyah Poonawala-Lohani, Purvi M Kakadia, Nicholas S Knowlton, Courtney Rh Lynch, Cho R Hong, Tet Woo Lee, Reidar A Grénman, Laura Caporiccio, Trevor D McKee, Mark Zaidi, Sehrish Butt, Andrew Mj Macann, Nicholas P McIvor, John M Chaplin, Kevin O Hicks, Stefan K Bohlander, Bradly G Wouters, Charles P Hart, Cristin G Print, William R Wilson, Michael A Curran, Francis W Hunter
Evofosfamide (TH-302) is a clinical-stage hypoxia-activated prodrug of a DNA-crosslinking nitrogen mustard that has potential utility for human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC), in which tumor hypoxia limits treatment outcome. We report the preclinical efficacy, target engagement, preliminary predictive biomarkers and initial clinical activity of evofosfamide for HPV-negative HNSCC. Evofosfamide was assessed in 22 genomically characterized cell lines and 7 cell line-derived xenograft (CDX), patient-derived xenograft (PDX), orthotopic, and syngeneic tumor models...
August 23, 2018: JCI Insight
Raymond J Cho, Ludmil B Alexandrov, Nicoline Y den Breems, Velina S Atanasova, Mehdi Farshchian, Elizabeth Purdom, Tran N Nguyen, Cristian Coarfa, Kimal Rajapakshe, Marco Prisco, Joya Sahu, Patrick Tassone, Evan J Greenawalt, Eric A Collisson, Wei Wu, Hui Yao, Xiaoping Su, Christina Guttmann-Gruber, Josefina Piñón Hofbauer, Raabia Hashmi, Ignacia Fuentes, Stephen C Benz, Justin Golovato, Erik A Ehli, Christel M Davis, Gareth E Davies, Kyle R Covington, Dedee F Murrell, Julio C Salas-Alanis, Francis Palisson, Anna L Bruckner, William Robinson, Cristina Has, Leena Bruckner-Tuderman, Matthias Titeux, Marcel F Jonkman, Elham Rashidghamat, Su M Lwin, Jemima E Mellerio, John A McGrath, Johann W Bauer, Alain Hovnanian, Kenneth Y Tsai, Andrew P South
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors...
August 22, 2018: Science Translational Medicine
Lluís Nisa, David Barras, Michaela Medová, Daniel M Aebersold, Matúš Medo, Michaela Poliaková, Jonas Koch, Beat Bojaxhiu, Olgun Eliçin, Matthias S Dettmer, Paolo Angelino, Roland Giger, Urs Borner, Marco D Caversaccio, Thomas E Carey, Liza Ho, Thomas A McKee, Mauro Delorenzi, Yitzhak Zimmer
Metastases and tumor recurrence have a major prognostic impact in head and neck squamous cell carcinoma (HNSCC); however, cellular models that comprehensively characterize metastatic and recurrent HNSCC are lacking. To this end, we obtained genomic, transcriptomic, and copy number profiles of the UM-SCC cell line panel, encompassing patient-matched metastatic and recurrent cells. UM-SCC cells recapitulate the most prevalent genomic alterations described in HNSCC, featuring common TP53, PI3K, NOTCH, and Hippo pathway mutations...
August 14, 2018: Molecular Cancer Research: MCR
Shu-Chun Lin, Li-Han Lin, Ssu-Yu Yu, Shou-Yen Kao, Kuo-Wei Chang, Hui-Wen Cheng, Chung-Ji Liu
In recent years, the incidence and mortality rates of head and neck squamous cell carcinoma (HNSCC) have increased worldwide. Therefore, understanding genomic alterations in HNSCC carcinogenesis is crucial for appropriate diagnosis and therapy. Procadherin FAT1, which encodes 4588 amino acid residues, regulates complex mechanisms to promote oncogenesis or suppression of malignancies. Multiplex polymerase chain reaction (PCR)-based next-generation sequencing (NGS) revealed FAT1 somatic mutations. The clinicopathologic implications of FAT1 in HNSCC were investigated using expression assays, and the functional role of FAT1 in HNSCC pathogenesis was determined using ectopic expression and knockdown experiments...
August 9, 2018: Carcinogenesis
Matt Lechner, Ankur R Chakravarthy, Vonn Walter, Liam Masterson, Andrew Feber, Amrita Jay, Paul M Weinberger, Richard A McIndoe, Cillian T Forde, Kerry Chester, Nicholas Kalavrezos, Paul O'Flynn, Martin Forster, Terry M Jones, Francis M Vaz, D Neil Hayes, Tim R Fenton
OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project...
August 2018: Oral Oncology
Yu-Ting Chen, Jian-Ni Yao, Yu-Tao Qin, Kai Hu, Fang Wu, Ye-Ying Fang
MicroRNAs (miRNAs) are confirmed to be tumor promoters or suppressors in multiple squamous cell carcinomas (SCCs). miR-99a-5p has been demonstrated to be downregulated in cancerous tissues, but its functional role in head and neck SCC (HNSCC) and its mechanism of action have not been fully elucidated. Here, we studied the expression of miR-99a-5p in HNSCC and performed a clinical value assessment and then extracted mature expression data from The Cancer Genome Atlas (TCGA) and microarrays from Gene Expression Omnibus (GEO)...
August 2018: FEBS Open Bio
Ching Ying Lin, Hyunwoo Kwon, Guillermo O Rangel Rivera, Xue Li, Dongjun Chung, Zihai Li
Background: Remarkable discrepancy exists in outcomes between men and women for multiple malignancies. We sought to expose sex differences in using platelet count and neutrophil-to-lymphocyte ratio (NLR) to predict overall survival for select cancer types with focus on head and neck squamous cell carcinoma (HNSCC). Methods: Peripheral blood samples from 9,365 patients seen in a tertiary teaching hospital with nine different primary tumors were retrospectively examined. HNSCC RNA-sequencing data from The Cancer Genome Atlas were analyzed by two computational means [Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE)] to extend our observations to the tumor microenvironment...
October 2018: Cancer Epidemiology, Biomarkers & Prevention
Ayman Oweida, Mohammad K Hararah, Andy Phan, David Binder, Shilpa Bhatia, Shelby Lennon, Sanjana Bukkapatnam, Benjamin Van Court, Nomin Uyanga, Laurel Darragh, Hyun Min Kim, David Raben, Aik Choon Tan, Lynn Heasley, Eric Clambey, Raphael Nemenoff, Sana D Karam
Purpose: Radiotherapy (RT) can transform the immune landscape and render poorly immunogenic tumors sensitive to PD-L1 inhibition. Here, we established that the response to combined RT and PD-L1 inhibition is transient and investigated mechanisms of resistance. Experimental Design: Mechanisms of resistance to RT and PD-L1 blockade were investigated in orthotopic murine head and neck squamous cell carcinoma (HNSCC) tumors using mass cytometry and whole-genome sequencing. Mice were treated with anti-PD-L1 or anti-TIM-3 alone and in combination with and without RT...
July 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alexandra Iulia Irimie, Cornelia Braicu, Roxana Cojocneanu, Lorand Magdo, Anca Onaciu, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Smaranda Buduru, Ioana Berindan-Neagoe
Smoking is a well-known behavior that has an important negative impact on human health, and is considered to be a significant factor related to the development and progression of head and neck squamous cell carcinomas (HNSCCs). Use of high-dimensional datasets to discern novel HNSCC driver genes related to smoking represents an important challenge. The Cancer Genome Atlas (TCGA) analysis was performed in three co-existing groups of HNSCC in order to assess whether gene expression landscape is affected by tobacco smoking, having quit, or non-smoking status...
July 23, 2018: International Journal of Environmental Research and Public Health
Vinay K Kartha, Khalid A Alamoud, Khikmet Sadykov, Bach-Cuc Nguyen, Fabrice Laroche, Hui Feng, Jina Lee, Sara I Pai, Xaralabos Varelas, Ann Marie Egloff, Jennifer E Snyder-Cappione, Anna C Belkina, Manish V Bais, Stefano Monti, Maria A Kukuruzinska
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments...
July 20, 2018: Genome Medicine
Jin Chen, Guiming Fu, Yibo Chen, Guiquan Zhu, Zhaohui Wang
Postoperative radiotherapy or concurrent chemoradiotherapy are routine clinical options for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the benefit of adding chemotherapy to radiotherapy is contested. The present study aimed to develop a gene signature to predict the clinical benefit of postoperative chemoradiotherapy using public data from The Cancer Genome Atlas. A 22-gene signature was established, which demonstrated the best predictive value. Patients were separated into low-score and high-score subgroups based on the expression score of the 22-gene signature...
August 2018: Oncology Letters
Henna Pehkonen, Mira Lento, Pernilla von Nandelstadh, Artemis Filippou, Reidar Grénman, Kaisa Lehti, Outi Monni
BACKGROUND: PPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-α1 encoded by PPF1A1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-α1 function in cancer progression has remained elusive. METHODS: Invasion regulating activity of liprin-α1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown...
July 13, 2018: Cell Communication and Signaling: CCS
Xiao-Nan Fang, Miao Yin, Hua Li, Cheng Liang, Cong Xu, Gui-Wen Yang, Hua-Xiang Zhang
Long non-coding RNAs (lncRNAs) can regulate gene expression directly or indirectly through interacting with microRNAs (miRNAs). However, the role of differentially expressed mRNAs, lncRNAs and miRNAs, and especially their related competitive endogenous RNAs (ceRNA) network in head and neck squamous cell carcinoma (HNSCC), is not fully comprehended. In this paper, the lncRNA, miRNA, and mRNA expression profiles of 546 HNSCC patients, including 502 tumor and 44 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) were analyzed...
July 12, 2018: Scientific Reports
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