scholarly journals CAFE MOCHA: An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer—An Example of Distant Metastasis– and Recurrence-Linked Classifiers in Head and Neck Squamous Cell Carcinoma

2018 ◽  
pp. 1-11
Author(s):  
Neeraja M. Krishnan ◽  
Mohanraj I ◽  
Janani Hariharan ◽  
Binay Panda
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
Cancer Type ◽  
Molecular Signatures ◽  
Molecular Changes ◽  
Statistical Framework

Purpose With large amounts of multidimensional molecular data on cancers generated and deposited into public repositories such as The Cancer Genome Atlas and International Cancer Genome Consortium, a cancer type agnostic and integrative platform will help to identify signatures with clinical relevance. We devised such a platform and showcase it by identifying a molecular signature for patients with metastatic and recurrent (MR) head and neck squamous cell carcinoma (HNSCC). Methods We devised a statistical framework accompanied by a graphical user interface–driven application, Clinical Association of Functionally Established MOlecular CHAnges ( CAFE MOCHA; https://github.com/binaypanda/CAFEMOCHA), to discover molecular signatures linked to a specific clinical attribute in a cancer type. The platform integrates mutations and indels, gene expression, DNA methylation, and copy number variations to discover a classifier first and then to predict an incoming tumor for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry–based algorithm called complete specificity margin-based clustering, which ensures maximum specificity. CAFE MOCHA classifies an incoming tumor sample using either its matched normal or a built-in database of normal tissues. The application is packed and deployed using the install4j multiplatform installer. We tested CAFE MOCHA in HNSCC tumors (n = 513) followed by validation in tumors from an independent cohort (n = 18) for discovering a signature linked to distant MR. Results CAFE MOCHA identified an integrated signature, MR44, associated with distant MR HNSCC, with 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage. Conclusion CAFE MOCHA is a cancer type and clinical attribute agnostic statistical framework to discover integrated molecular signatures.

scholarly journals CAFE MOCHA:An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer; an Example of Distant Metastasis and Recurrence-linked Classifiers in Head and Neck Squamous Cell Carcinoma

2017 ◽  
Author(s):  
Neeraja M Krishnan ◽  
I Mohanraj ◽  
Janani Hariharan ◽  
Binay Panda
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Distant Metastasis ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Signature ◽  
Cancer Type ◽  
Molecular Changes ◽  
Statistical Framework

AbstractBackgroundCAFE MOCHA(Clinical Association of Functionally Established MOlecular CHAnges) is an integrated GUI-driven computational and statistical framework to discover molecular signatures linked to a specific clinical attribute in a cancer type. We testedCAFE MOCHAin head and neck squamous cell carcinoma (HNSCC) for discovering a signature linked to distant metastasis and recurrence (MR) in 517 tumors from TCGA and validated the signature in 18 tumors from an independent cohort.MethodsThe platform integrates mutations and indels, gene expression, DNA methylation and copy number variations to discover a classifier first, predict an incoming tumour for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry-based algorithm, called Complete Specificity Margin Based Clustering (CSMBC) with 100% specificity.CAFE MOCHAclassifies an incoming tumour sample using either a matched normal or a built-in database of normal tissues. The application is packed and deployed using theinstall4jmulti-platform installer.ResultsWe testedCAFE MOCHAto discover a signature for distant metastasis and recurrence in HNSCC. The signature MR44 in HNSCC yielded 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage.ConclusionsCAFE MOCHAis a cancer type- and clinical attribute-agnostic computational and statistical framework to discover integrated molecular signature for a specific clinical attribute.CAFE MOCHAis available in GitHub (https://github.com/binaypanda/CAFEMOCHA).

scholarly journals Clinical correlation of opposing molecular signatures in head and neck squamous cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Fatima Qadir ◽  
Anand Lalli ◽  
Huma Habib Dar ◽  
Sungjae Hwang ◽  
Hebah Aldehlawi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Signatures ◽  
Clinical Correlation

MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: A systematic review and meta-analysis

Oral Oncology ◽  
2015 ◽  
Vol 51 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zahra Jamali ◽  
Naser Asl Aminabadi ◽  
Rana Attaran ◽  
Fatemeh Pournagiazar ◽  
Sina Ghertasi Oskouei ◽  
...  
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Meta Analysis ◽  
Human Head ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Signatures

scholarly journals Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1018
Author(s):  
Florencia Veigas ◽  
Yamil D. Mahmoud ◽  
Joaquin Merlo ◽  
Adriana Rinflerch ◽  
Gabriel Adrian Rabinovich ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune System ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Predictive Biomarkers ◽  
Neck Squamous Cell Carcinoma ◽  
Cancer Type

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives.

Significance of TP53 mutation in treatment and prognosis in head and neck squamous cell carcinoma

2021 ◽  
Vol 15 (1) ◽  
pp. 15-28
Author(s):  
Yu Jin ◽  
Xing Qin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tp53 Mutation ◽  
Cox Regression ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Background: TP53 is ranked as the most common mutated gene in head and neck squamous cell carcinoma (HNSCC). Results: The status of TP53 mutation was investigated on International Cancer Genome Consortium and The Cancer Genome Atlas database and TP53-related differentially expressed genes were screened out from transcriptome data and mutation information. A TP53-related prognostic gene signature ( TIMP4, ONECUT2, CGNL1, DMRTA2 and NKX2.3) was constructed based on Cox regression analysis and LASSO algorithm. Univariate and multivariate analyses were carried out to identify promising prognosticators for HNSCC. Conclusion: Our findings provide a well-rounded landscape of TP53 mutation in HNSCC and pave the groundwork for developing innovative and effective cancer treatment methods for HNSCC.

scholarly journals HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Dan Long ◽  
Li Xu ◽  
Zeyi Deng ◽  
Dandan Guo ◽  
Yangchun Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Cancer Type ◽  
Luciferase Reporter Gene ◽  
Hpv16 E6

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignant cancer type worldwide. Radiosensitivity has been shown to be significantly increased in patients with human papillomavirus (HPV)-positive HNSCC compared with HPV-negative patients. However, the clinical significance of HPV and its regulatory mechanisms in HNSCC are largely unknown. The aim of our study was to explore the regulatory mechanism of miR-27a-3p in the radiosensitivity of HPV-positive HNSCC cells. Methods E6-overexpressing and E6-knockdown HNSCC cell lines were generated and the transfection efficiencies were evaluated by quantitative real-time PCR (RT-qPCR) and western blotting. The expression of miR-27a-3p and DiGeorge syndrome critical region 8 (DGCR8) was examined by RT-qPCR after transfection with E6 overexpressing plasmid or E6 siRNA. The effects of miR-27a-3p on the radiosensitivity of HNSCC cells were explored by a colony formation and TUNEL staining assays. Bioinformatic tools and luciferase reporter assays were used to identify that SMG1 is the direct target of miR-27a-3p. Furthermore, the effect of E6 overexpression on the regulation of the miR-27a-3p/SMG1 axis was investigated. Results In our study, we found overexpression of HPV E6 upregulated the expression of DGCR8 and miR-27a-3p in HNSCC cells. We next confirmed that DGCR8 positively regulated the expression of miR-27a-3p in HNSCC cells. The luciferase reporter gene results verified that miR-27a-3p targeted the 3’UTR of SMG1 mRNA. MiR-27a-3p mimics transfection resulted in a decrease in SMG1 expression and miR-27a-3p inhibitor transfection increased SMG1 expression. Apoptotic activity of HNSCC cells was significantly increased in miR-27a-3p mimics HNSCC cells compared with control HNSCC cells. After treatment with 4 Gy irradiation, UM-SCC47 cells transfected with miR-27a-3p inhibitor or SMG1 overexpressing plasmid formed more colonies than the corresponding control cells. Furthermore, the rescue experiments demonstrated that HPV16 E6 improved the radiosensitivity of HNSCC cells by targeting miR-27a-3p/SMG1. Conclusion Our study demonstrated that HPV16 E6 activated the DGCR8/miR-27a-3p/SMG1 axis to enhance the radiosensitivity. Our findings might provide a novel therapeutic target to improve the response of HNSCC to radiotherapy.

scholarly journals Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Cai Yang ◽  
Hongxiang Mei ◽  
Liang Peng ◽  
Fulin Jiang ◽  
Bingjie Xie ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Signature ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Related Gene ◽  
Hpv Status

Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan–Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients’ overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.

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