Development of a five-protein signature for predicting the prognosis of head and neck squamous cell carcinoma

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Abstract

Currently no reliable indicators are available for predicting the clinical outcome of head and neck squamous cell carcinoma (HNSCC). This study aimed to develop a protein-based model to improve the prognosis prediction of HNSCC. The proteome data of HNSCC cohort was downloaded from The Cancer Proteome Atlas (TCPA) portal. The TCPA HNSCC cohort was randomly divided into the discovery and validation cohort. A protein-based risk signature was developed with the discovery cohort, and then verified with the validation cohort. The prognostic value of HER3_pY1289 was further determined. We have constructed a five-protein risk signature which was strongly associated with the overall survival (OS) in the discovery cohort. Similar findings were observed in the validation cohort. The protein-based risk signature was identified as an independent prognostic factor for HNSCC. A nomogram model built on the protein-based risk signature exhibited good performance for predicting OS. Our immunohistochemistry (IHC) analysis showed that higher HER3_pY1289 staining intensity was closely associated with unfavorable prognosis of HNSCC. HER3 suppression inhibited the proliferation and invasion capacity of HNSCC cells. Collectively, we have developed a protein-based risk signature for accurately predicting the prognosis of HNSCC, which might provide valuable information for optimal individualized treatment regimens.

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Most cited references 24

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Head and neck cancer.

Athanassios Argiris, Michalis V. Karamouzis, David Raben … (2008)

Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.

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mTOR kinase structure, mechanism and regulation by the rapamycin-binding domain

Haijuan Yang, Derek Rudge, Joseph Koos … (2013)

The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a truncated mTOR-mLST8 complex with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and mechanism remarkably similar to canonical protein kinases. The active site is highly recessed due to the FKBP12-Rapamycin binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR activating mutations map to the structural framework that holds these elements in place, indicating the kinase is controlled by restricted access. In vitro biochemistry indicates that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. FKBP12-rapamycin inhibits by directly blocking substrate recruitment and by further restricting active site access. The structures also reveal active site residues and conformational changes that underlie inhibitor potency and specificity.

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Correlation of mRNA and protein in complex biological samples.

Luis Serrano, Marc Guell, Tobias Maier (2009)

The correlation between mRNA and protein abundances in the cell has been reported to be notoriously poor. Recent technological advances in the quantitative analysis of mRNA and protein species in complex samples allow the detailed analysis of this pathway at the center of biological systems. We give an overview of available methods for the identification and quantification of free and ribosome-bound mRNA, protein abundances and individual protein turnover rates. We review available literature on the correlation of mRNA and protein abundances and discuss biological and technical parameters influencing the correlation of these central biological molecules.

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Author and article information

Journal

Journal ID (nlm-ta): Aging (Albany NY)

Journal ID (publisher-id): Aging

Title: Aging (Albany NY)

Publisher: Impact Journals

ISSN (Electronic): 1945-4589

Publication date Collection: 15 October 2020

Publication date (Electronic): 13 October 2020

Volume: 12

Issue: 19

Pages: 19740-19755

Affiliations

[1 ]Stomatological Hospital, Southern Medical University, Guangzhou 510280, China

[2 ]UCLA School of Dentistry, Los Angeles, CA 90095, USA

Author notes

[*]

Co-author

Correspondence to: Xinyuan Zhao; email: zhaoxinyuan1989@smu.edu.cn

Correspondence to: Li Cui; email: zsucllj@ucla.edu

Article

Publisher ID: 104036

DOI: 10.18632/aging.104036

PMC ID: 7732293

PubMed ID: 33049713

SO-VID: 3301f342-9c2c-4e91-bdb9-684b21318878

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Development of a five-protein signature for predicting the prognosis of head and neck squamous cell carcinoma

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In vitro alveolar region models

Most cited references 24

Head and neck cancer.

mTOR kinase structure, mechanism and regulation by the rapamycin-binding domain

Correlation of mRNA and protein in complex biological samples.

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