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Hnscc genomics

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 Omar Rangel Rivera, Xue Li, Dongjun Chung, Zihai Li
BACKGROUND: Remarkable discrepancy exists in outcomes between men/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 9365 patients seen in a tertiary teaching hospital with nine different primary tumors were retrospectively examined...
July 26, 2018: Cancer Epidemiology, Biomarkers & Prevention
Ayman Oweida, Mohammad Hararah, Andy V Phan, David C 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 T Clambey, Raphael A Nemenoff, Sana D Karam
PURPOSE: Radiation therapy (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 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
Daniel Martin, Maria S Degese, Lynn Vitale-Cross, Ramiro Iglesias-Bartolome, Juan Luis Callejas Valera, Zhiyong Wang, Xiaodong Feng, Huwate Yeerna, Vachan Vadmal, Toshiro Moroishi, Rick F Thorne, Moraima Zaida, Bradford Siegele, Sok C Cheong, Alfredo A Molinolo, Yardena Samuels, Pablo Tamayo, Kun Liang Guan, Scott M Lippman, J Guy Lyons, J Silvio Gutkind
Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FAT1 alterations (29...
July 9, 2018: Nature Communications
Shomereeta Roy, Souvick Roy, Madhabananda Kar, Shweta Thakur, Yusuf Akhter, Amit Kumar, Francesco Delogu, Swatishree Padhi, Arka Saha, Birendranath Banerjee
TRF2 is a telomere binding protein, a component of the shelterin complex that plays a major role in maintaining the integrity of the genome. TRF2 is over-expressed in a number of human cancers including Head and Neck cancer and might play a key role in tumor initiation and development. p38 MAPK signaling pathway is strongly activated in response to various environmental and cellular stresses and thus overexpressed in most of the Head and Neck cancer cases. In this study, we investigated potential interactions of TRF2 with p38 in HNSCC cells and patient samples...
July 9, 2018: Oncogenesis
Tatiana Lepikhova, Piia-Riitta Karhemo, Riku Louhimo, Bhagwan Yadav, Astrid Murumägi, Evgeny Kulesskiy, Mikko Kivento, Harri Sihto, Reidar Grénman, Stina M Syrjänen, Olli Kallioniemi, Tero Aittokallio, Krister Wennerberg, Heikki Joensuu, Outi Monni
There is an unmet need for effective targeted therapies for patients with advanced head and neck squamous cell carcinoma (HNSCC). We correlated gene expression, gene copy numbers and point mutations in 45 human papillomavirus negative HNSCC cell lines with the sensitivity to 220 anticancer drugs to discover predictive associations to genetic alterations. The drug response profiles revealed diverse efficacy of the tested drugs across the cell lines. Several genomic abnormalities and gene expression differences were associated with response to mTOR, MEK and EGFR inhibitors...
July 3, 2018: Molecular Cancer Therapeutics
Chao Liu, Theresa Guo, Guorong Xu, Akihiro Sakai, Shuling Ren, Takahito Fukusumi, Mizuo Ando, Sayed H Sadat, Yuki Saito, Zubair Khan, Kathleen M Fisch, Joseph Califano
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and alternative splicing is considered to play important roles in tumor progression. Our study is designed to identify alternative splicing events (ASEs) in HPV negative HNSCC. EXPERIMENTAL DESIGN: RNA sequencing data of 407 HPV negative HNSCC and 38 normal samples were obtained from The Cancer Genome Atlas (TCGA) and splice junctions were discovered using MapSplice...
June 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Esma Saada-Bouzid, Gérard Milano, Juliette Thariat
Squamous cell carcinomas are the most frequent subgroup among head and neck malignant tumors (HNSCC). Tobacco (±alcohol) and HPV infection, the two main risk factors, define two entities with distinct anatomo-clinical and genetic features. HPV-positive, non-tobacco-related HNSCCs are associated with a better prognosis, a rather simple genomic profile, frequent activating mutations of genes involved in pi3kinase-pathway, and the scarcity of mutations of tumor suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more complex, are characterized by almost mandatory inactivating mutations/deletions of tumor suppressor genes (TP53, CDKN2A) and the possible, but less frequent, activating mutations or amplifications of some oncogenes that encode for cell cycle proteins or receptors with tyrosine kinase activity...
June 21, 2018: Bulletin du Cancer
Jeesoo Chae, Weon Seo Park, Min Jung Kim, Se Song Jang, Dongwan Hong, Junsun Ryu, Chang Hwan Ryu, Ji-Hyun Kim, Moon-Kyung Choi, Kwan Ho Cho, Sung Ho Moon, Tak Yun, Jong-Il Kim, Yuh-Seog Jung
Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015...
June 25, 2018: BMB Reports
Hoi-Lam Ngan, Lan Wang, Kwok-Wai Lo, Vivian Wai Yan Lui
: Epstein-Barr virus-positive nasopharyngeal carcinoma (EBV(+) NPC), and human papillomavirus-positive head and neck squamous cell carcinoma (HPV(+) HNSCC) are two distinct types of aggressive head and neck cancers with early age onsets. Their recently identified genomic landscapes by whole-exome sequencing (WES) clearly reveal critical roles of: (1) inflammation via NF-kB activation, (2) survival via PI3K aberrations, and perhaps (3) immune evasion via MHC loss in these cancers as summarized in this review...
June 21, 2018: Cancers
Shan Jin, Min-Da Liu, Hong Wu, Pai Pang, Song Wang, Zhen-Ning Li, Chang-Fu Sun, Fa-Yu Liu
Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed accompanied by lymph node metastasis. C-C chemokine receptor type 7 (CCR7) is associated with the invasion and metastasis of tumors in HNSCC through various signaling pathways. The role of hsa-miR-125a-5p in HNSCC remains unclear. The present study was performed to investigate the association between hsa-miR-125a-5p and CCR7 in HNSCC. Reverse transcription-quantitative polymerase chain reaction was applied to analyze the expression of hsa-miR-125a-5p in clinical samples...
June 2018: Oncology Letters
Tania Islam, Rezanur Rahman, Esra Gov, Beste Turanli, Gizem Gulfidan, Anwarul Haque, Kazım Yalçın Arga, Nurul Haque Mollah
The head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but robust biomarkers and diagnostics are still not available. This study provides in-depth insights from systems biology analyses to identify molecular biomarker signatures to inform systematic drug targeting in HNSCC. Gene expression profiles from tumors and normal tissues of 22 patients with histological confirmation of nonmetastatic HNSCC were subjected to integrative analyses with genome-scale biomolecular networks (i...
June 2018: Omics: a Journal of Integrative Biology
Chongchang Zhou, Meng Ye, Shumin Ni, Qun Li, Dong Ye, Jinyun Li, Zhishen Shen, Hongxia Deng
DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
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