Dataset Information

New Insights into the impact of Human Papillomavirus on Oral Cancer in Young Patients: Proteomic Approach Reveals a Novel Role for S100A8

ABSTRACT: Human Papillomavirus (HPV) infection has been recently linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and/ progression are poorly understood. Methods: We perform a MS-based proteomic profiling based on HPV status on OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (-) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival in contrast to A2M and Serpine1, which low levels show association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rate, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor which, when activated, triggered S100A8 and NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern, distinctively of HPV (-), involving expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses that had important consequences in prognosis and may guide therapeutic decisions.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Head And Neck Squamous Cell Carcinoma Cell

SUBMITTER: Adriana Franco Paes Leme

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD041856 | Pride | 2023-07-20

REPOSITORIES: Pride

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			Action	DRS
	01dez_Marisol_200min_cid_12.raw	Raw
	01dez_Marisol_200min_cid_16.raw	Raw
	01dez_Marisol_200min_cid_5.raw	Raw
	01dez_Marisol_200min_cid_6.raw	Raw
	13jan_Marisol_16.raw	Raw

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New Insights into the Impact of Human Papillomavirus on Oral Cancer in Young Patients: Proteomic Approach Reveals a Novel Role for S100A8.

Miranda-Galvis Marisol M Carneiro Soares Carolina C Moretto Carnielli Carolina C Ramalho Buttura Jaqueline J Sales de Sá Raisa R Kaminagakura Estela E Marchi Fabio Albuquerque FA Paes Leme Adriana Franco AF Lópes Pinto Clóvis A CA Santos-Silva Alan Roger AR Moraes Castilho Rogerio R Kowalski Luiz Paulo LP Squarize Cristiane Helena CH

Cells 20230505 9

Human papillomavirus (HPV) infection has recently been linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and progression are poorly understood.<h4>Methods</h4>We performed MS-based proteomics profiling based on HPV status in OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape.<h4>Results</h4>Thirty-nine proteins are differ ...[more]

PMID: 37174723

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Project description:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.