Dataset Information

Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis.

ABSTRACT: This study represents a proteomic resource for HNSCC and SQCLC with quantitative protein expression data for 7800 proteins and provides a proteomic diagnostic signature for classification for undetermined secondary lung tumors in HNSCC patients. By quantitative mass-spectrometry-based proteomics, we characterized a cohort of 63 squamous cell carcinomas of the lung (SQCLC), 49 of the head and neck region (HNSCC) and 51 HNSCC-correlated lung tumors with squamous cell histology that evolved in the course of the disease.

INSTRUMENT(S): Q Exactive HF-X, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

SUBMITTER: Kuan-Ting Pan

LAB HEAD: Thomas Oellerich

PROVIDER: PXD007705 | Pride | 2018-08-06

REPOSITORIES: Pride

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Publications

Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis.

Bohnenberger Hanibal H Kaderali Lars L Ströbel Philipp P Yepes Diego D Plessmann Uwe U Dharia Neekesh V NV Yao Sha S Heydt Carina C Merkelbach-Bruse Sabine S Emmert Alexander A Hoffmann Jonatan J Bodemeyer Julius J Reuter-Jessen Kirsten K Lois Anna-Maria AM Dröge Leif Hendrik LH Baumeister Philipp P Walz Christoph C Biggemann Lorenz L Walter Roland R Häupl Björn B Comoglio Federico F Pan Kuan-Ting KT Scheich Sebastian S Lenz Christof C Küffer Stefan S Bremmer Felix F Kitz Julia J Sitte Maren M Beißbarth Tim T Hinterthaner Marc M Sebastian Martin M Lotz Joachim J Schildhaus Hans-Ulrich HU Wolff Hendrik H Danner Bernhard C BC Brandts Christian C Büttner Reinhard R Canis Martin M Stegmaier Kimberly K Serve Hubert H Urlaub Henning H Oellerich Thomas T

EMBO molecular medicine 20180901 9

Patients with head-and-neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentiall ...[more]

PMID: 30097507

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Project description:Head and neck squamous cell carcinoma (HNSCC) is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies for HNSCC and the understanding of its biology both depend upon clinically relevant animal models. An increasingly promising xenograft model, the patient derived xenograft (PDX), is developed by surgically implanting tumor tissue directly from a patient into an immunocompromised mouse. We transplanted 30 HNSCC primary tumors directly into mice. The histology and stromal components were analyzed using immunohistochemistry. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines. Five of 30 (17%) transplanted tumors could be serially passaged and used for therapeutic and mechanistic studies. One cell line has been established from a tongue primary. The tumors maintained the histologic appearance of the parent tumor although human stromal components were lost upon engraftment. One PDX model was derived from an HPV-positive tumor. From the >54,000 probes tested, there were widespread differences in gene expression between the tumors growing in mice vs. the corresponding human tumors from which they were derived. For genes differing between parent tumors and human cell lines in culture, the PDXs’ expression pattern was very similar to that of the parent tumors. There were also widespread expression differences between the human tumors that subsequently grew in mice vs. those that did not - suggesting that this model enriches for cancers with distinct biological features. Our results demonstrate the feasibility of a PDX model of HNSCC. Gene expression patterns suggest that the PDX more closely recapitulated the parental tumor than do cells in culture. The histology of the tumors in mice is similar to that of the same tumor in humans. Additionally, gene expression patterns and histology are stable over multiple generations. We transplanted HNSCC primary tumors directly into mice. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines.

Dataset Information

Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis.

Publications

Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis.

Similar Datasets

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