Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness

Daniel L. Pouliquen
* ORCID logo ,
Joanna Kopecka
ORCID logo ,
Stéphanie Blandin
,
Alice Boissard
,
Cécile Henry
,
Chiara Riganti
ORCID logo ,
Catherine Guette
Version 1 : Received: 23 May 2023 / Approved: 24 May 2023 / Online: 24 May 2023 (05:06:41 CEST)

How to cite: Pouliquen, D.L.; Kopecka, J.; Blandin, S.; Boissard, A.; Henry, C.; Riganti, C.; Guette, C. Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness. Preprints 2023, 2023051698. https://doi.org/10.20944/preprints202305.1698.v1 Pouliquen, D.L.; Kopecka, J.; Blandin, S.; Boissard, A.; Henry, C.; Riganti, C.; Guette, C. Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness. Preprints 2023, 2023051698. https://doi.org/10.20944/preprints202305.1698.v1

Abstract

Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

Keywords

Cancer; Aggressiveness; Mitochondria; Acadvl; Fatty acid beta oxidation; Biomarker; Proteomics; Malignant mesothelioma

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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