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In-depth proteomic ...
In-depth proteomic analysis reveals unique subtype-specific signatures in human small-cell lung cancer
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- Szeitz, Beáta (författare)
- Semmelweis University
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- Megyesfalvi, Zsolt (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Woldmar, Nicole (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Federal University of Rio de Janeiro
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- Valkó, Zsuzsanna (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Schwendenwein, Anna (författare)
- Medical University of Vienna
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- Bárány, Nándor (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Paku, Sándor (författare)
- Semmelweis University
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- László, Viktória (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Kiss, Helga (författare)
- Semmelweis University
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- Bugyik, Edina (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Lang, Christian (författare)
- Medical University of Vienna
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- Szász, Attila Marcell (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Pizzatti, Luciana (författare)
- Federal University of Rio de Janeiro
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- Bogos, Krisztina (författare)
- National Korányi Institute for Tuberculosis and Pulmonology, Hungary
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- Hoda, Mir Alireza (författare)
- Medical University of Vienna
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- Hoetzenecker, Konrad (författare)
- Medical University of Vienna
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- Marko-Varga, György (författare)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Horvatovich, Peter (författare)
- University of Groningen
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- Döme, Balázs (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine,National Korányi Institute for Tuberculosis and Pulmonology, Hungary,Medical University of Vienna,Semmelweis University
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- Schelch, Karin (författare)
- Medical University of Vienna
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- Rezeli, Melinda (författare)
- Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups
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(creator_code:org_t)
- 2022-09-23
- 2022
- Engelska.
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 12:9, s. 1060-1060
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Small-cell lung cancer (SCLC) molecular subtypes have been primarily characterized based on the expression pattern of the following key transcription regulators: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). Here, we investigated the proteomic landscape of these molecular subsets with the aim to identify novel subtype-specific proteins of diagnostic and therapeutic relevance.METHODS: Pellets and cell media of 26 human SCLC cell lines were subjected to label-free shotgun proteomics for large-scale protein identification and quantitation, followed by in-depth bioinformatic analyses. Proteomic data were correlated with the cell lines' phenotypic characteristics and with public transcriptomic data of SCLC cell lines and tissues.RESULTS: Our quantitative proteomic data highlighted that four molecular subtypes are clearly distinguishable at the protein level. The cell lines exhibited diverse neuroendocrine and epithelial-mesenchymal characteristics that varied by subtype. A total of 367 proteins were identified in the cell pellet and 34 in the culture media that showed significant up- or downregulation in one subtype, including known druggable proteins and potential blood-based markers. Pathway enrichment analysis and parallel investigation of transcriptomics from SCLC cell lines outlined unique signatures for each subtype, such as upregulated oxidative phosphorylation in SCLC-A, DNA replication in SCLC-N, neurotrophin signalling in SCLC-P and epithelial-mesenchymal transition in SCLC-Y. Importantly, we identified the YAP1-driven subtype as the most distinct SCLC subgroup. Using sparse partial least squares discriminant analysis, we identified proteins that clearly distinguish four SCLC subtypes based on their expression pattern, including potential diagnostic markers for SCLC-Y (e.g. GPX8, PKD2 and UFO).CONCLUSIONS: We report for the first time, the protein expression differences among SCLC subtypes. By shedding light on potential subtype-specific therapeutic vulnerabilities and diagnostic biomarkers, our results may contribute to a better understanding of SCLC biology and the development of novel therapies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Biomarkers
- Cell Line, Tumor
- Culture Media
- Gene Expression Regulation, Neoplastic/genetics
- Humans
- Lung Neoplasms/drug therapy
- Nerve Growth Factors/genetics
- Peroxidases/genetics
- Proteomics
- Small Cell Lung Carcinoma/genetics
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Szeitz, Beáta
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Megyesfalvi, Zso ...
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Woldmar, Nicole
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Valkó, Zsuzsanna
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Schwendenwein, A ...
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Bárány, Nándor
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Paku, Sándor
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László, Viktória
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Kiss, Helga
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Bugyik, Edina
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Lang, Christian
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Szász, Attila Ma ...
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Pizzatti, Lucian ...
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Bogos, Krisztina
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Hoda, Mir Alirez ...
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Hoetzenecker, Ko ...
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Marko-Varga, Gyö ...
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Horvatovich, Pet ...
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Döme, Balázs
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Schelch, Karin
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Rezeli, Melinda
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