Identification of carcinogenesis and tumor progression processes in pancreatic ductal adenocarcinoma using high-throughput proteomics
Author
Trilla-Fuertes, Lucía; Gámez Pozo, Angelo; Lumbreras-Herrera, María Isabel; López-Vacas, Rocío; Heredia-Soto, Victoria; Ghanem, Ismael; López-Camacho, Elena; Zapater-Moros, Andrea; Miguel, María; Peña-Burgos, Eva M.; Palacios, Elena; de Uribe, Marta; Guerra, Laura; Dittmann, Antje; Mendiola, Marta; Vara, Juan Ángel Fresno; Feliú Batlle, JaimeEntity
UAM. Departamento de MedicinaPublisher
MDPIDate
2022-05-13Citation
10.3390/cancers14102414
Cancers 14.10 (2022): 2414
ISSN
2072-6694 (online)DOI
10.3390/cancers14102414Funded by
This research was funded by EPIC-XS, project number 823839, the Horizon 2020 programme of the European Union, and ISCIII PI18/01604Project
info:eu-repo/grantAgreement/EC/H2020/823839; Gobierno de España. PI18/01604Editor's Version
https://doi.org/10.3390/cancers14102414Subjects
carcinogenesis; high-throughput proteomics; molecular profiles; pancreatic ductal adenocarcinoma; tumor progression; MedicinaRights
© 2022 by the authorsAbstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an overall 5-year survival rate of just 5%. A better understanding of the carcinogenesis processes and the mechanisms of the progression of PDAC is mandatory. Fifty-two PDAC patients treated with surgery and adjuvant therapy, with available primary tumors, normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases, were selected for the study. Proteins were extracted from small punches and analyzed by LC-MS/MS using data-independent acquisition. Proteomics data were analyzed using probabilistic graphical models, allowing functional characterization. Comparisons between groups were made using linear mixed models. Three proteomic tumor subtypes were defined. T1 (32% of patients) was related to adhesion, T2 (34%) had metabolic features, and T3 (34%) presented high splicing and nucleoplasm activity. These proteomics subtypes were validated in the PDAC TCGA cohort. Relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. Carcinogenesis in the T1 subtype seems to be related to an increase of adhesion and complement activation node activity, whereas tumor progression seems to be related to nucleoplasm and translation nodes. Regarding the T2 subtype, it seems that metabolism and, especially, mitochondria act as the motor of cancer development. T3 analyses point out that nucleoplasm, mitochondria and metabolism, and extracellular matrix nodes could be involved in T3 tumor carcinogenesis. The identified processes were different among proteomics subtypes, suggesting that the molecular motor of the disease is different in each subtype. These differences can have implications for the development of future tailored therapeutic approaches for each PDAC proteomics subtype
Files in this item
Google Scholar:Trilla-Fuertes, Lucía
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Gámez Pozo, Angelo
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Lumbreras-Herrera, María Isabel
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López-Vacas, Rocío
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Heredia-Soto, Victoria
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Ghanem, Ismael
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López-Camacho, Elena
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Zapater-Moros, Andrea
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Miguel, María
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Peña-Burgos, Eva M.
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Palacios, Elena
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de Uribe, Marta
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Guerra, Laura
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Dittmann, Antje
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Mendiola, Marta
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Vara, Juan Ángel Fresno
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Feliú Batlle, Jaime
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