Interaction between potential doubling time and TP53 mutation: predicting radiotherapy outcome in squamous cell carcinoma of the head and neck

Objectives: The role of proteins of Cajal bodies (CB) and its identical twin, Gemini of coiled bodies (GEMs) in maintaining genomic integrity and its influence on the initiation, progression, and prognosis of head and neck squamous cell carcinoma (HNSCC) is gaining attention. We attempted to identify the CB and GEM-associated proteins (CB-GEMs) expression in HNSCC patients and study the influence of gender, TP53 mutation, age, and tobacco use on such expression. Material and Methods: TP53 mutation, tobacco use, gender, and mRNA levels of CB-GEM proteins of 520 HNSCC cases were collected and subjected to differential expression (DE) analysis. The resultant DE genes were used to create a transcriptional factor gene network using encode chip sequential data. Pathway analysis of the network was performed and presented. P ≤ 0.05 was taken as significant. Results: For smoking, the genes GEMIN8, FMR1, TRIM22, and FBL emerged as significantly DE genes. For gender, EAF1, GEMIN8, ZC3H8, TRIM22, FBL, LSG1, ZNF473, GMNC, GEMIN2, ISG20, Opa interacting protein 5, GMNN, and CDK2 were DE gene with statistical significance. For TP53, 15 genes were DE with statistical significance. Transcriptional misregulation in cancer was the frequently affected pathway. The CB-GEM bodies are effective highly conserved, splicesomal organelles that are needed for proper mRNA assembly. Certain mRNA of proteins of the CB-GEM bodies is influenced by TP53 status, gender, and tobacco use. Conclusion: The DE of CB-GEM bodies related protein in HNSCC patients are presented. Furthermore, we identified certain critical pathways, where the DE genes of CB-GEM bodies exert critical influence on HNSCC characteristics. This could potentially alter the HNSCC progression, treatment response, and prognosis.

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Evaluation of computational tools to determine prognostic significance of TP53 mutation in head and neck squamous cell carcinoma (HNSCC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.6035 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 6035-6035

Author(s):

David Masica ◽

Shuli Li ◽

Chris Douville ◽

Judith Manola ◽

Robert L. Ferris ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Computational Tools

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Imaging-Genomic Study of Head and Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes and Genomic Mechanisms via Integration of The Cancer Genome Atlas and The Cancer Imaging Archive

JCO Clinical Cancer Informatics ◽

10.1200/cci.18.00073 ◽

2019 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Yitan Zhu ◽

Abdallah S.R. Mohamed ◽

Stephen Y. Lai ◽

Shengjie Yang ◽

Aasheesh Kanwar ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

The Cancer Genome Atlas ◽

Genomic Features ◽

Cancer Genome Atlas ◽

Genome Atlas

Purpose Recent data suggest that imaging radiomic features of a tumor could be indicative of important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. We performed a comprehensive study to discover the imaginggenomic associations in head and neck squamous cell carcinoma (HNSCC) and explore the potential of predicting tumor genomic alternations using radiomic features. Methods Our retrospective study integrated whole-genome multiomics data from The Cancer Genome Atlas with matched computed tomography imaging data from The Cancer Imaging Archive for the same set of 126 patients with HNSCC. Linear regression and gene set enrichment analysis were used to identify statistically significant associations between radiomic imaging and genomic features. Random forest classifier was used to predict the status of two key HNSCC molecular biomarkers, human papillomavirus and disruptive TP53 mutation, on the basis of radiomic features. Results Widespread and statistically significant associations were discovered between genomic features (including microRNA expression, somatic mutations, and transcriptional activity, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of human papillomavirus and TP53 mutation status using radiomic features achieved areas under the receiver operating characteristic curve of 0.71 and 0.641, respectively. Conclusion Our exploratory study suggests that radiomic features are associated with genomic characteristics at multiple molecular layers in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

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Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients

Annals of Oncology ◽

10.1093/annonc/mdt380 ◽

2013 ◽

Vol 24 (12) ◽

pp. 3082-3088 ◽

Cited By ~ 47

Author(s):

F. Ganci ◽

A. Sacconi ◽

N. Bossel Ben-Moshe ◽

V. Manciocco ◽

I. Sperduti ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

Neck Squamous Cell Carcinoma

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TP53 Mutation as Molecular Marker in the Assessment of Surgical Margin Status in Head and Neck Squamous Cell Carcinoma

Nepalese Journal of Cancer ◽

10.3126/njc.v5i1.41317 ◽

2021 ◽

Vol 5 (1) ◽

pp. 27-32

Author(s):

Asmita Rayamajhi ◽

Bibek Acharya ◽

B. Khanal

Keyword(s):

Squamous Cell Carcinoma ◽

Local Recurrence ◽

Tumor Suppressor ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

Surgical Margin ◽

Neck Squamous Cell Carcinoma ◽

Molecular Technique

Genetic alteration of tumor suppressor and oncogene plays important role in development and progression of cancer. Tumor suppressor gene, Tp53 also knows as ‘guardian of genome’ has very important role in head and neck squamous cell carcinoma (HNSCC). Mutation of Tp53 has been commonly observed in other carcinomas including HNSCC, comprising of 75-85% of head and neck cancer, with highest in larynx and hypopharynx followed by oral cavity. Tp53 mutation is more commonly seen in Human Papilloma Virus (HPV)-ve and wild type Tp53 in HPV+ve carcinomas. Role of Tp53 mutation help us to know about the prognostic state, molecular stage and chance of local recurrence. Different studies have highlighted the importance of assessing Tp53 mutation in the negative surgical margin, which showed mutation of Tp53 in the negative surgical margin resulted increase in chance of local recurrence. These studies provide significance of moving conventional method of histopathological assessment to molecular assessment, that gives advantage of proper management decision as well as prognosis of tumor. Regarding techniques of these assessments, molecular technique has been always superior to immunohistochemistry (IHC) but is somewhat tedious, so more clinical analysis on the alternatives of IHC combined with Next generation sequencing (NGS) gives the platform to perform more Tp53 mutation test in the surgical margin. This is the need of time to incorporate molecular staging in the conventional staging for proper treatment and outcome in the management of head and neck cancers.

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