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Hnscc genomics

Irene Arroyo-Solera, Miguel Ángel Pavón, Xavier León, Montserrat López, Alberto Gallardo, María Virtudes Céspedes, Isolda Casanova, Víctor Pallarès, Antonio López-Pousa, María Antonia Mangues, Agustí Barnadas, Miquel Quer, Ramón Mangues
BACKGROUND: Serpin Family E Member 1 (SerpinE1) overexpression associates with poor clinical outcome in head and neck squamous cell carcinoma (HNSCC) patients. This study analyzed the role of serpinE1 in HNSCC dissemination. METHODS: We studied the phenotypic characteristics and dissemination of HNSCC cells overexpressing serpinE1 using an orthotopic model and the association between serpinE1 overexpression and clinicopathological variables in patients included in The Cancer Genome Atlas database...
December 12, 2018: Head & Neck
Pengfei Diao, Yue Song, Han Ge, Yaping Wu, Jin Li, Wei Zhang, Yanling Wang, Jie Cheng
Deregulated long noncoding RNAs (lncRNA) have been critically implicated in tumorigenesis and serve as novel diagnostic and prognostic biomarkers. Here we sought to develop a prognostic lncRNA signature in patients with head and neck squamous cell carcinoma (HNSCC). Original RNA-seq data of 499 HNSCC samples were retrieved from The Cancer Genome Atlas database, which was randomly divided into training and testing set. Univariate Cox regression survival analysis, robust likelihood-based survival model and random sampling iterations were applied to identify prognostic lncRNA candidates in the training cohort...
December 11, 2018: Journal of Cellular Biochemistry
Ah Ra Jung, Young-Gyu Eun, Young Chan Lee, Joo Kyung Noh, Kee Hwan Kwon
Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases...
December 12, 2018: International Journal of Molecular Sciences
Bo Li, Jie Zhu, Lei Meng
Actin‑like protein 8 (ACTL8) is a member of the cancer‑testis antigens (CTA) family, which is mainly localized in the cytoplasm and generally expressed in the testis. The association between ACTL8 and various types of cancer, including glioblastoma and breast cancer, has previously been demonstrated. However, whether ACTL8 is involved in the development of head and neck squamous cell carcinoma (HNSCC) remains unknown. In the present study, the expression of ACTL8 in patients with HNSCC was analyzed in The Cancer Genome Atlas (TCGA) dataset, clinical tissues and cell lines...
December 3, 2018: Molecular Medicine Reports
Megan L Ludwig, Aditi Kulkarni, Andrew C Birkeland, Nicole L Michmerhuizen, Susan K Foltin, Jacqueline E Mann, Rebecca C Hoesli, Samantha N Devenport, Brittany M Jewell, Andrew G Shuman, Matthew E Spector, Thomas E Carey, Hui Jiang, J Chad Brenner
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...
December 2018: Oral Oncology
Francisco Hermida-Prado, Sofía T Menéndez, Pablo Albornoz-Afanasiev, Rocío Granda-Diaz, Saúl Álvarez-Teijeiro, M Ángeles Villaronga, Eva Allonca, Laura Alonso-Durán, Xavier León, Laia Alemany, Marisa Mena, Nagore Del-Rio-Ibisate, Aurora Astudillo, René Rodríguez, Juan P Rodrigo, Juana M García-Pedrero
Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN , CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients...
December 1, 2018: Journal of Clinical Medicine
Rita Das, Jamie Coupar, Paul E Clavijo, Anthony Saleh, Tsu-Fan Cheng, Xinping Yang, Jianhong Chen, Carter Van Waes, Zhong Chen
Head and neck squamous cell carcinomas (HNSCC) preferentially spread to regional cervical tissues and lymph nodes. Here, we hypothesized that lymphotoxin-β (LTβ), receptor LTβR, and NF-κB-inducing kinase (NIK), promote the aberrant activation of alternative NF-κB2/RELB pathway and genes, that enhance migration and invasion of HNSCC. Genomic and expression alterations of the alternative NF-kB pathway were examined in 279 HNSCC tumors from The Cancer Genome Atlas (TCGA) and a panel of HNSCC lines. LTβR is amplified or overexpressed in HNSCC of the larynx or oral cavity, while LTβ, NIK, and RELB are overexpressed in cancers arising within lymphoid oropharyngeal and tonsillar sites...
November 22, 2018: Molecular Carcinogenesis
Haihe Gao, Lisha Li, Mang Xiao, Yongwei Guo, Yi Shen, Lixin Cheng, Ming Tang
Purpose: DKK1 is an antagonist of the Wnt signaling pathway that has various roles in human physiology. Notably, aberrant DKK1 expression is observed in several cancers. In this retrospective study, we assessed the association between DKK1 expression levels and head and neck squamous cell carcinoma (HNSCC) and its prognostic value. Materials and methods: Using RNA-seq data from HNSCC tumors (N=520) and adjacent normal tissue (N=44) in The Cancer Genome Atlas, we evaluated DKK1 expression levels...
2018: Cancer Management and Research
Prasenjit Chakraborty, Tanusri Karmakar, Neeraj Arora, Geetashree Mukherjee
Head and neck squamous cell carcinoma (HNSCC) is responsible for a large number of deaths each year. Oral cancer is the most frequent subtype of HNSCC. Historically, oral cancer has been associated with an increase in the consumption of tobacco and alcohol products, seen especially in the Asian subcontinent. It has also been associated with infection by the human papilloma virus (HPV), particularly strain HPV16. Treatment usually involves a multidisciplinary approach of surgery combined with chemotherapy and radiation...
October 2018: Heliyon
Prashant V Bommi, Sriram Ravindran, Pradip Raychaudhuri, Srilata Bagchi
DDB2 is a sensor of DNA damage and it plays an important role in Global Genomic Repair (GG-NER). Our previous studies show that DDB2 is involved in the regulation of metastasis in colon adenocarcinoma. Squamous Cell Carcinomas in the Oral/Head & Neck region (HNSCC) are particularly aggressive due to high incidence of recurrence and distant metastasis. In this study, we show that DDB2 expression is downregulated in advanced HNSCCs and loss of DDB2 expression coincides with reduced survival. Recent meta-analysis of gene expression data characterized the mesenchymal-type (EMT-type) as one most aggressive cancer cluster in HNSCC...
October 5, 2018: Oncotarget
Zuzana Saidak, Florian Clatot, Denis Chatelain, Antoine Galmiche
OBJECTIVES: Perineural invasion (PNI) is a common histopathological finding in head and neck squamous cell carcinoma (HNSCC). We aimed to explore the molecular mechanisms involved in PNI and the role of PNI as an aggressive pathological feature. MATERIALS AND METHODS: We used data from The Cancer Genome Atlas (TCGA) to relate the histological presentation of 528 HNSCC tumours to clinical, whole genome expression and proteomic data. RESULTS: We identified a specific gene expression profile highly enriched in genes related to muscle differentiation/function and associated with PNI in HNSCC...
November 2018: Oral Oncology
David M Vossen, Caroline V M Verhagen, Reidar Grénman, Roelof J C Kluin, Marcel Verheij, Michiel W M van den Brekel, Lodewyk F A Wessels, Conchita Vens
BACKGROUND: Large cancer genome studies continue to reveal new players in treatment response and tumorigenesis. The discrimination of functional alterations from the abundance of passenger genetic alterations still poses challenges and determines DNA sequence variant selection procedures. Here we evaluate variant selection strategies that select homozygous variants and rare SNPs and assess its value in detecting tumor cells with DNA repair defects. METHODS: To this end we employed a panel of 29 patient-derived head and neck squamous cell carcinoma (HNSCC) cell lines, of which a subset harbors DNA repair defects...
2018: PloS One
Farshid Fathi, Zahra Faghih, Bijan Khademi, Toomaj Kayedi, Nasrollah Erfani, Abbas Gahderi
INTRODUCTION: Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of head and neck and the sixth most common malignancy worldwide. Programmed cell death 1 (PD-1) is an immune inhibitory molecule which through interaction with its ligands recruits protein phosphatase resulting in immune response inhibition. Expression of PD-1 ligands on tumor cells is considered as one of the crucial immune evasion mechanisms. This study aimed to investigate the association of PD-1 gene polymorphisms at positions PD1...
October 30, 2018: Immunological Investigations
Peng Wang, Meng Jin, Chuan-Hui Sun, Like Yang, Yu-Shan Li, Xin Wang, Ya-Nan Sun, Lin-Li Tian, Ming Liu
Increasing evidence has shown that long non-coding RNAs (lncRNAs) have important biological functions and can be used as a prognostic biomarker in human cancers. However, investigation of the prognostic value of lncRNAs in head and neck squamous cell carcinoma (HNSCC) is in infancy. In the present study, we analyzed the lncRNA expression data in a large number of HNSCC patients ( n =425) derived from The Cancer Genome Atlas (TCGA) to identify an lncRNA expression signature for improving the prognosis of HNSCC...
December 21, 2018: Bioscience Reports
Adriana Pitea, Ivan Kondofersky, Steffen Sass, Fabian J Theis, Nikola S Mueller, Kristian Unger
Copy number aberrations (CNAs) are known to strongly affect oncogenes and tumour suppressor genes. Given the critical role CNAs play in cancer research, it is essential to accurately identify CNAs from tumour genomes. One particular challenge in finding CNAs is the effect of confounding variables. To address this issue, we assessed how commonly used CNA identification algorithms perform on SNP 6.0 genotyping data in the presence of confounding variables. We simulated realistic synthetic data with varying levels of three confounding variables-the tumour purity, the length of a copy number region and the CNA burden (the percentage of CNAs present in a profiled genome)-and evaluated the performance of OncoSNP, ASCAT, GenoCNA, GISTIC and CGHcall...
October 23, 2018: Briefings in Bioinformatics
Wenjuan Zhang, Yupei Liang, Lihui Li, Xiaofang Wang, Zi Yan, Changsheng Dong, Mu-Sheng Zeng, Qian Zhong, Xue-Kui Liu, Jinha Yu, Shuyang Sun, Xiaojun Liu, Jihui Kang, Hu Zhao, Lak Shin Jeong, Yanmei Zhang, Lijun Jia
OBJECTIVES: The present study aimed to reveal expression status of the neddylation enzymes in HNSCC and to elucidate the anticancer efficacy and the underlying mechanisms of inhibiting neddylation pathway. MATERIALS AND METHODS: The expression levels of neddylation enzymes were estimated by Western blotting in human HNSCC specimens and bioinformatics analysis of the cancer genome atlas (TCGA) database. Cell apoptosis was evaluated by Annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) stain and fluorescence-activated cell sorting (FACS)...
October 19, 2018: Cell Proliferation
Raquel L Costa, Mariana Boroni, Marcelo A Soares
The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter...
October 15, 2018: Scientific Reports
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...
November 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
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