Dataset Information

Multisite proteome provides insights into the biology and prognostic markers for head and neck cancer

ABSTRACT: The poor prognosis of head and neck cancer (HNC) is largely associated with the presence of metastasis in the lymph nodes (LN). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. The protein profiles are strictly associated with immune modulation across datasets, which provided the basis to investigate immune markers associated with metastasis. The proteome of LN metastasis cells quite recapitulates the proteome of primary sites. Conversely, the LN microenvironment proteome highlights candidate markers. By integrating selected markers at peptide, protein, and transcript levels with machine learning models, we indicate a nodal metastasis signature in blood and saliva. In summary, we present the deepest proteome characterization of multiple sampling sites in HNC, providing a promising basis to understand tumoral biology and indicating metastasis-associated biomarkers.

ORGANISM(S): Homo Sapiens

SUBMITTER: Adriana Paes Leme

PROVIDER: PXD027984 | panorama | Tue Nov 22 00:00:00 GMT 2022

REPOSITORIES: PanoramaPublic

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Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer.

Busso-Lopes Ariane F AF Neves Leandro X LX Câmara Guilherme A GA Granato Daniela C DC Pretti Marco Antônio M MAM Heberle Henry H Patroni Fábio M S FMS Sá Jamile J Yokoo Sami S Rivera César C Domingues Romênia R RR Normando Ana Gabriela C AGC De Rossi Tatiane T Mello Barbara P BP Galdino Nayane A L NAL Pauletti Bianca A BA Lacerda Pammela A PA Rodrigues André Afonso N AAN Casarim André Luis M ALM de Lima-Souza Reydson A RA Damas Ingrid I II Mariano Fernanda V FV Gollob Kenneth J KJ Medina Tiago S TS Cervigne Nilva K NK Prado-Ribeiro Ana Carolina AC Brandão Thaís Bianca TB Villa Luisa L LL Uno Miyuki M Boroni Mariana M Kowalski Luiz Paulo LP González-Arriagada Wilfredo Alejandro WA Paes Leme Adriana F AF

Nature communications 20221107 1

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis fo ...[more]

PMID: 36344512

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Project description:Head and neck squamous cell carcinoma (HNSCC) often present with locoregional or distant disease, despite multimodal therapeutic approaches, which include surgical resection, chemoradiotherapy, and more recently immunotherapy for metastatic, or recurrent HNSCC. Therapies often target the primary and nodal regional HNSCC sites, and efficacy at controlling occult distant sites remains poor. Whilst our understanding of the tumour microenvironment, conducive for effective therapies is increasing, the biology underpinning locoregional sites remains unclear. Here, we applied targeted spatial proteomic approaches to primary and lymph node metastasis from an oropharyngeal SCC (OPSCC) cohort, to understand the expression of proteins within tumour, and stromal compartments of the respective sites in both matched and unmatched patients’ samples. In unmatched analyses of n=43 primary and 11 nodal metastasis, our data indicated that tumour cells in nodal metastases had higher levels of Ki-67, PARP, BAD and cleaved caspase 9, suggesting a role for increased proliferation, DNA repair and apoptosis within these metastatic cells. Conversely, in matched analyses (n=7), pro-apoptotic markers BIM and BAD were enriched in the stroma of primary tumours. Univariate, overall survival (OS) analysis indicated CD25 in tumour regions of primary tumours to be associated with reduced survival (HR=3.3, p=0.003), while partial response (PR) was associated with an improved OS (HR=0.33, p=0.015). This study highlights the utility of spatial proteomics for delineating tumour and stroma compartment composition, and the utility towards understanding these properties in locoregional metastasis. These findings indicate the unique biological properties of lymph node metastases that may elucidate further understanding of the subsequent distant metastatic potential of OPSCC. In this dataset, we applied GeoMx DSP protein profiling to tumour and tumour microenvironment regions of primary and lymphnode metastasis FFPE samples. The files here represent the Ncounter readout from this assay.

Project description:Objective: The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies. Methods: A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays,and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner.The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC . Results: Analysed by Illumina mRNA microarrays,there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1,CDK2,CDK4,MCM2,MCM3,MCM4) were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR. Conclusions: The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. The result will contribute to the understanding of the molecular basis of LSCC and help to improve diagnosis and treatment. A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays,and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner.The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC .

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Dataset Information

Multisite proteome provides insights into the biology and prognostic markers for head and neck cancer

Publications

Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer.

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