14 results on '"Nicole Woldmar"'
Search Results
2. Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts
- Author
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Leticia Szadai, Aron Bartha, Indira Pla Parada, Alexandra I.T. Lakatos, Dorottya M.P. Pál, Anna Sára Lengyel, Natália Pinto de Almeida, Ágnes Judit Jánosi, Fábio Nogueira, Beata Szeitz, Viktória Doma, Nicole Woldmar, Jéssica Guedes, Zsuzsanna Ujfaludi, Zoltán Gábor Pahi, Tibor Pankotai, Yonghyo Kim, Balázs Győrffy, Bo Baldetorp, Charlotte Welinder, A. Marcell Szasz, Lazaro Betancourt, Jeovanis Gil, Roger Appelqvist, Ho Jeong Kwon, Sarolta Kárpáti, Magdalena Kuras, Jimmy Rodriguez Murillo, István Balázs Németh, Johan Malm, David Fenyö, Krzysztof Pawłowski, Peter Horvatovich, Elisabet Wieslander, Lajos V. Kemény, Gilberto Domont, György Marko-Varga, and Aniel Sanchez
- Subjects
metastatic melanoma ,immunotherapy ,immunotherapy response ,responders ,non-responders ,proteomics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.MethodsEvaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.ResultsSix proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort.DiscussionOur study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.
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- 2024
- Full Text
- View/download PDF
3. Mitochondrial and immune response dysregulation in melanoma recurrence
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Leticia Szadai, Jéssica de Siqueira Guedes, Nicole Woldmar, Natália Pinto deAlmeida, Ágnes Judit Jánosi, Ahmad Rajeh, Ferenc Kovács, András Kriston, Ede Migh, Guihong Wan, Nga Nguyen, Henriett Oskolás, Roger Appelqvist, Fábio CN Nogueira, Gilberto B Domont, Kun‐Hsing Yu, Eugene R. Semenov, Johan Malm, Melinda Rezeli, Elisabet Wieslander, David Fenyö, Lajos Kemény, Peter Horvath, István Balázs Németh, György Marko‐Varga, and Jeovanis Gil
- Subjects
Medicine (General) ,R5-920 - Published
- 2023
- Full Text
- View/download PDF
4. In‐depth proteomic analysis reveals unique subtype‐specific signatures in human small‐cell lung cancer
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Beáta Szeitz, Zsolt Megyesfalvi, Nicole Woldmar, Zsuzsanna Valkó, Anna Schwendenwein, Nándor Bárány, Sándor Paku, Viktória László, Helga Kiss, Edina Bugyik, Christian Lang, Attila Marcell Szász, Luciana Pizzatti, Krisztina Bogos, Mir Alireza Hoda, Konrad Hoetzenecker, György Marko‐Varga, Peter Horvatovich, Balázs Döme, Karin Schelch, and Melinda Rezeli
- Subjects
diagnostic biomarkers ,molecular targets ,proteomics ,secretome ,small‐cell lung cancer ,subtype ,Medicine (General) ,R5-920 - Abstract
Abstract 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.
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- 2022
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- View/download PDF
5. The human melanoma proteome atlas—Defining the molecular pathology
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Lazaro Hiram Betancourt, Jeovanis Gil, Yonghyo Kim, Viktória Doma, Uğur Çakır, Aniel Sanchez, Jimmy Rodriguez Murillo, Magdalena Kuras, Indira Pla Parada, Yutaka Sugihara, Roger Appelqvist, Elisabet Wieslander, Charlotte Welinder, Erika Velasquez, Natália Pinto deAlmeida, Nicole Woldmar, Matilda Marko‐Varga, Krzysztof Pawłowski, Jonatan Eriksson, Beáta Szeitz, Bo Baldetorp, Christian Ingvar, Håkan Olsson, Lotta Lundgren, Henrik Lindberg, Henriett Oskolas, Boram Lee, Ethan Berge, Marie Sjögren, Carina Eriksson, Dasol Kim, Ho Jeong Kwon, Beatrice Knudsen, Melinda Rezeli, Runyu Hong, Peter Horvatovich, Tasso Miliotis, Toshihide Nishimura, Harubumi Kato, Erik Steinfelder, Madalina Oppermann, Ken Miller, Francesco Florindi, Qimin Zhou, Gilberto B. Domont, Luciana Pizzatti, Fábio C. S. Nogueira, Peter Horvath, Leticia Szadai, József Tímár, Sarolta Kárpáti, A. Marcell Szász, Johan Malm, David Fenyö, Henrik Ekedahl, István Balázs Németh, and György Marko‐Varga
- Subjects
heterogeneity ,histopathology ,metastatic malignant melanoma ,proteogenomics ,subcellular localization ,Medicine (General) ,R5-920 - Abstract
Abstract The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
- Published
- 2021
- Full Text
- View/download PDF
6. The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome
- Author
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Lazaro Hiram Betancourt, Jeovanis Gil, Aniel Sanchez, Viktória Doma, Magdalena Kuras, Jimmy Rodriguez Murillo, Erika Velasquez, Uğur Çakır, Yonghyo Kim, Yutaka Sugihara, Indira Pla Parada, Beáta Szeitz, Roger Appelqvist, Elisabet Wieslander, Charlotte Welinder, Natália Pinto deAlmeida, Nicole Woldmar, Matilda Marko‐Varga, Jonatan Eriksson, Krzysztof Pawłowski, Bo Baldetorp, Christian Ingvar, Håkan Olsson, Lotta Lundgren, Henrik Lindberg, Henriett Oskolas, Boram Lee, Ethan Berge, Marie Sjögren, Carina Eriksson, Dasol Kim, Ho Jeong Kwon, Beatrice Knudsen, Melinda Rezeli, Johan Malm, Runyu Hong, Peter Horvath, A. Marcell Szász, József Tímár, Sarolta Kárpáti, Peter Horvatovich, Tasso Miliotis, Toshihide Nishimura, Harubumi Kato, Erik Steinfelder, Madalina Oppermann, Ken Miller, Francesco Florindi, Quimin Zhou, Gilberto B. Domont, Luciana Pizzatti, Fábio C. S. Nogueira, Leticia Szadai, István Balázs Németh, Henrik Ekedahl, David Fenyö, and György Marko‐Varga
- Subjects
acetylation stoichiometry ,BRAF ,driver mutations ,histopathology ,metastatic melanoma ,phosphorylation ,Medicine (General) ,R5-920 - Abstract
Abstract The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease.
- Published
- 2021
- Full Text
- View/download PDF
7. Toxicoproteomics Disclose Pesticides as Downregulators of TNF-α, IL-1β and Estrogen Receptor Pathways in Breast Cancer Women Chronically Exposed
- Author
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Luciana Pizzatti, Aedra Carla Bufalo Kawassaki, Bruna Fadel, Fabio C. S. Nogueira, Joseph A. M. Evaristo, Nicole Woldmar, Géssica Tuani Teixeira, Janaína Carla Da Silva, Thalita Basso Scandolara, Daniel Rech, Luciano Pessôa Zanetti Candiotto, Guilherme Ferreira Silveira, Wander Rogério Pavanelli, and Carolina Panis
- Subjects
breast cancer ,toxicoproteomics ,tumor necrosis factor alfa ,interleukin beta 1 ,estrogen signaling ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Deleterious effects have been widely associated with chronic pesticide exposure, including cancer development. In spite of several known consequences that pesticides can trigger in the human body, few is known regarding its impact on breast cancer women that are chronically exposed to such substances during agricultural work lifelong. In this context, the present study performed a high-throughput toxicoproteomic study in association with a bioinformatics-based design to explore new putative processes and pathways deregulated by chronic pesticide exposure in breast cancer patients. To reach this goal, we analyzed comparatively non-depleted plasma samples from exposed (n = 130) and non-occupationally exposed (n = 112) women diagnosed with breast cancer by using a label-free proteomic tool. The list of proteins differentially expressed was explored by bioinformatics and the main pathways and processes further investigated. The toxicoproteomic study revealed that women exposed to pesticides exhibited mainly downregulated events, linked to immune response, coagulation and estrogen-mediated events in relation to the unexposed ones. Further investigation shown that the identified deregulated processes and pathways correlated with significant distinct levels tumor necrosis factor alpha and interleukin 1 beta in the blood, and specific clinicopathological characteristics pointed out by bioinformatics analysis as adipose-trophic levels, menopause and intratumoral clots formation. Altogether, these findings reinforce pesticides as downregulators of several biological process and highlight that these compounds can be linked to poor prognosis in breast cancer.
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- 2020
- Full Text
- View/download PDF
8. Proteomic Workflows for High-Quality Quantitative Proteome and Post-Translational Modification Analysis of Clinically Relevant Samples from Formalin-Fixed Paraffin-Embedded Archives
- Author
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Jeovanis Gil, János Fillinger, György Marko-Varga, Melinda Rezeli, Nicole Woldmar, Luciana Pizzatti, Magdalena Kuras, Judit Moldvay, Johan Malm, Max Hefner, Yonghyo Kim, and Balazs Dome
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Proteomics ,0301 basic medicine ,Tissue Fixation ,Proteome ,Lysine ,Computational biology ,Biochemistry ,Post Translational Modification Analysis ,Workflow ,03 medical and health sciences ,Formaldehyde ,Protein purification ,Humans ,Prospective Studies ,Biomarker discovery ,Paraffin Embedding ,030102 biochemistry & molecular biology ,Chemistry ,Reproducibility of Results ,General Chemistry ,Isobaric labeling ,030104 developmental biology ,Acetylation ,Protein Processing, Post-Translational - Abstract
Well-characterized archival formalin-fixed paraffin-embedded (FFPE) tissues are of much value for prospective biomarker discovery studies, and protocols that offer high throughput and good reproducibility are essential in proteomics. Therefore, we implemented efficient paraffin removal and protein extraction from FFPE tissues followed by an optimized two-enzyme digestion using suspension trapping (S-Trap). The protocol was then combined with TMTpro 16plex labeling and applied to lung adenocarcinoma patient samples. In total, 9585 proteins were identified, and proteins related to the clinical outcome were detected. Because acetylation is known to play a major role in cancer development, a fast on-trap acetylation protocol was developed for studying endogenous lysine acetylation, which allows identification and localization of the lysine acetylation together with quantitative comparison between samples. We demonstrated that FFPE tissues are equivalent to frozen tissues to study the degree of acetylation between patients. In summary, we present a reproducible sample preparation workflow optimized for FFPE tissues that resolves known proteomic-related challenges. We demonstrate compatibility of the S-Trap with isobaric labeling and for the first time, we prove that it is feasible to study endogenous lysine acetylation stoichiometry in FFPE tissues, contributing to better utility of the existing global tissue archives. The MS proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD020157, PXD021986, and PXD021964.
- Published
- 2020
9. Mapping the Melanoma Plasma Proteome (MPP) Using Single-Shot Proteomics Interfaced with the WiMT Database
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Sanchez, Natália Almeida, Jimmy Rodriguez, Indira Pla Parada, Yasset Perez-Riverol, Nicole Woldmar, Yonghyo Kim, Henriett Oskolas, Lazaro Betancourt, Jeovanis Gil Valdés, K. Barbara Sahlin, Luciana Pizzatti, A. Marcell Szasz, Sarolta Kárpáti, Roger Appelqvist, Johan Malm, Gilberto B. Domont, Fábio C. S. Nogueira, György Marko-Varga, and Aniel
- Subjects
malignant melanoma ,plasma ,proteome ,proteomics ,biomarkers ,WiMT - Abstract
Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.
- Published
- 2021
- Full Text
- View/download PDF
10. Mapping the Melanoma Plasma Proteome (MPP) Using Single-Shot Proteomics Interfaced with the WiMT Database
- Author
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Natália Almeida, Jimmy Rodriguez, Indira Pla Parada, Yasset Perez-Riverol, Nicole Woldmar, Yonghyo Kim, Henriett Oskolas, Lazaro Betancourt, Jeovanis Gil Valdés, K. Barbara Sahlin, Luciana Pizzatti, A. Marcell Szasz, Sarolta Kárpáti, Roger Appelqvist, Johan Malm, Gilberto B. Domont, Fábio C. S. Nogueira, György Marko-Varga, and Aniel Sanchez
- Subjects
proteomics ,proteome ,malignant melanoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biomarkers ,WiMT ,RC254-282 ,Article ,plasma - Abstract
Simple Summary We developed a clinical proteomics methodology, known as Wise MS Transfer (WiMT), for deep identification of blood proteins in undepleted plasma samples. We applied it to the analysis of undepleted melanoma plasma samples as a proof of principle. Malignant melanoma is the most aggressive type of skin cancer, and early diagnostic and prognostic predictors are essential to establish the most suitable treatment tailored to the patient. Our results showed the greatest identification of proteins and biological processes to date reported for a “dilute and shoot” approach within plasma samples from melanoma patients. More than 1200 proteins related to key biological processes in melanoma progression were mapped, including signaling (the PI3K–Akt signaling pathway), immune system processes (complement and coagulation cascade), and secretion (exosome proteins). These proteins and related biological processes constitute the core of blood components that could be monitored by mass spectrometry in clinical proteomic studies from undepleted plasma samples in melanoma. Abstract Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.
- Published
- 2021
11. The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome
- Author
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Ethan Berge, Quimin Zhou, Peter Horvatovich, Marie Sjögren, Natália Pinto de Almeida, Erika Velasquez, Matilda Marko-Varga, Madalina Oppermann, Lázaro Betancourt, Jonatan Eriksson, Magdalena Kuras, Jeovanis Gil, Luciana Pizzatti, Yonghyo Kim, Fábio C. S. Nogueira, Indira Pla Parada, Nicole Woldmar, Jimmy Rodriguez Murillo, Viktória Doma, Gilberto B. Domont, István Németh, József Tímár, Sarolta Kárpáti, Leticia Szadai, Runyu Hong, Toshihide Nishimura, Johan Malm, Melinda Rezeli, Håkan Olsson, Charlotte Welinder, A. Marcell Szász, Henrik Lindberg, Uğur Çakır, Krzysztof Pawłowski, Christian Ingvar, Yutaka Sugihara, Elisabet Wieslander, Erik Steinfelder, Tasso Miliotis, Francesco Florindi, Ho Jeong Kwon, Ken Miller, David Fenyö, Peter Horvath, Boram Lee, György Marko-Varga, Bo Baldetorp, Aniel Sanchez, Lotta Lundgren, Henrik Ekedahl, Henriett Oskolas, Dasol Kim, Beáta Szeitz, Roger Appelqvist, Beatrice S. Knudsen, Harubumi Kato, Carina Eriksson, Analytical Biochemistry, and Medicinal Chemistry and Bioanalysis (MCB)
- Subjects
Proteomics ,Proto-Oncogene Proteins B-raf ,Medicine (General) ,Databases, Factual ,Proteome ,driver mutations ,Medicine (miscellaneous) ,Antineoplastic Agents ,Computational biology ,Biology ,Genome ,DNA sequencing ,Cell Line ,BRAF ,Transcriptome ,R5-920 ,Tandem Mass Spectrometry ,medicine ,Human proteome project ,Humans ,Melanoma ,Gene ,Research Articles ,Chromatography, High Pressure Liquid ,phosphorylation ,Blood Proteins ,Proteogenomics ,medicine.disease ,posttranslational‐modification ,proteogenomics ,Mutation ,histopathology ,Molecular Medicine ,Protein Processing, Post-Translational ,acetylation stoichiometry ,Research Article ,metastatic melanoma - Abstract
The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease., The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. This data covers 65% and 74% of the predicted and identified human proteome, respectively.
- Published
- 2021
12. The human melanoma proteome atlas—Defining the molecular pathology
- Author
-
Marie Sjögren, Lázaro Betancourt, Natália Pinto de Almeida, Charlotte Welinder, Jeovanis Gil, Uğur Çakır, Madalina Oppermann, Elisabet Wieslander, Roger Appelqvist, Ken Miller, David Fenyö, Carina Eriksson, Leticia Szadai, Matilda Marko-Varga, A. Marcell Szász, Toshihide Nishimura, Peter Horvatovich, Erika Velasquez, Luiciana Pizzatti, Sarolta Kárpáti, Peter Horvath, Henrik Lindberg, Viktória Doma, Christian Ingvar, Magdalena Kuras, Nicole Woldmar, Jimmy Rodriguez Murillo, Gilberto B. Domont, István Németh, Yonghyo Kim, Runyu Hong, Indira Pla Parada, Håkan Olsson, Johan Malm, Ho Jeong Kwon, Fábio C. S. Nogueira, Yutaka Sugihara, Erik Steinfelder, Jonatan Eriksson, Bo Baldetorp, Ethan Berge, Aniel Sanchez, József Tímár, Krzysztof Pawłowski, Tasso Miliotis, György Marko-Varga, Henriett Oskolas, Francesco Florindi, Dasol Kim, Lotta Lundgren, Melinda Rezeli, Boram Lee, Beatrice S. Knudsen, Harubumi Kato, Henrik Ekedahl, Qimin Zhou, Beáta Szeitz, Analytical Biochemistry, and Medicinal Chemistry and Bioanalysis (MCB)
- Subjects
Adult ,Male ,Proteomics ,Medicine (General) ,medicine.medical_specialty ,Skin Neoplasms ,Proteome ,Medicine (miscellaneous) ,metastatic malignant melanoma ,Biology ,Young Adult ,R5-920 ,Tandem Mass Spectrometry ,Cell Line, Tumor ,subcellular localization ,Human proteome project ,medicine ,Humans ,Melanoma ,Research Articles ,Chromatography, High Pressure Liquid ,Aged ,Aged, 80 and over ,Molecular pathology ,Cancer ,Middle Aged ,medicine.disease ,Subcellular localization ,Proteogenomics ,proteogenomics ,Cancer research ,histopathology ,Molecular Medicine ,Histopathology ,Female ,heterogeneity ,Research Article - Abstract
The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients., The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and sub‐cellular localization was annotated within both primary and metastatic melanoma.
- Published
- 2021
13. Gene doping and genomic science in sports: where are we?
- Author
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João Meirelles, Monica Costa Padilha, Francisco Radler de Aquino Neto, Luciana Pizzatti, Henrique Pereira, Nicole Woldmar, Bruna Fadel, Gabriella Poralla, Vanessa Rayol, Sheila López, and Mariana Figueiredo
- Subjects
0301 basic medicine ,Doping in Sports ,Clinical Biochemistry ,Genetic Diseases, Inborn ,Gene transfer ,General Medicine ,Genetic Therapy ,Analytical Chemistry ,03 medical and health sciences ,Medical Laboratory Technology ,030104 developmental biology ,0302 clinical medicine ,Gene doping ,Athletes ,Healthy individuals ,Hereditary Diseases ,Agency (sociology) ,Humans ,Engineering ethics ,Elite athletes ,Business ,Genetic Testing ,General Pharmacology, Toxicology and Pharmaceutics ,human activities ,030217 neurology & neurosurgery - Abstract
The misuse of sport-related gene transfer methods in elite athletes is a real and growing concern. The success of gene therapy in the treatment of hereditary diseases has been most evident since targets in gene therapy products can be used in healthy individuals to improve sports performance. Performing these practices threatens the sporting character of competitions and may pose potential health hazards. Since the World Anti-Doping Agency pronouncement on the prohibition of such practices in 2003, several researchers have been trying to address the challenge of developing an effective method for the detection of genetic doping. This review presents an overview of the published methods developed for this purpose, the advantages and limitations of technologies and the putative target genes. At last, we present the perspective related to the application of the detection methods in the doping control field.
- Published
- 2020
14. Toxicoproteomics Disclose Pesticides as Downregulators of TNF-α, IL-1β and Estrogen Receptor Pathways in Breast Cancer Women Chronically Exposed
- Author
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Joseph Albert Medeiros Evaristo, Aedra Carla Bufalo Kawassaki, Luciano Pessôa Zanetti Candiotto, Géssica Tuani Teixeira, Daniel Rech, Carolina Panis, Luciana Pizzatti, Guilherme Ferreira Silveira, Janaína Carla da Silva, Nicole Woldmar, Fábio C. S. Nogueira, Wander Rogério Pavanelli, Thalita Basso Scandolara, and Bruna Fadel
- Subjects
0301 basic medicine ,Cancer Research ,Estrogen receptor ,Context (language use) ,lcsh:RC254-282 ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Immune system ,Breast cancer ,tumor necrosis factor alfa ,medicine ,estrogen signaling ,Original Research ,business.industry ,toxicoproteomics ,Pesticide ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,interleukin beta 1 ,Menopause ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Tumor necrosis factor alpha ,Cancer development ,business - Abstract
Deleterious effects have been widely associated with chronic pesticide exposure, including cancer development. In spite of several known consequences that pesticides can trigger in the human body, few is known regarding its impact on breast cancer women that are chronically exposed to such substances during agricultural work lifelong. In this context, the present study performed a high-throughput toxicoproteomic study in association with a bioinformatics-based design to explore new putative processes and pathways deregulated by chronic pesticide exposure in breast cancer patients. To reach this goal, we analyzed comparatively non-depleted plasma samples from exposed (n = 130) and non-occupationally exposed (n = 112) women diagnosed with breast cancer by using a label-free proteomic tool. The list of proteins differentially expressed was explored by bioinformatics and the main pathways and processes further investigated. The toxicoproteomic study revealed that women exposed to pesticides exhibited mainly downregulated events, linked to immune response, coagulation and estrogen-mediated events in relation to the unexposed ones. Further investigation shown that the identified deregulated processes and pathways correlated with significant distinct levels tumor necrosis factor alpha and interleukin 1 beta in the blood, and specific clinicopathological characteristics pointed out by bioinformatics analysis as adipose-trophic levels, menopause and intratumoral clots formation. Altogether, these findings reinforce pesticides as downregulators of several biological process and highlight that these compounds can be linked to poor prognosis in breast cancer.
- Published
- 2020
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