Oncotarget

Research Papers:

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients

Michela Terlizzi, Antonio Molino, Chiara Colarusso, Pasquale Somma, Ilaria De Rosa, Jacopo Troisi, Giovanni Scala, Rosario Salvi, Aldo Pinto and Rosalinda Sorrentino _

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Oncotarget. 2020; 11:3515-3525. https://doi.org/10.18632/oncotarget.27724

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Abstract

Michela Terlizzi1,2,*, Antonio Molino3,*, Chiara Colarusso1,2, Pasquale Somma4, Ilaria De Rosa4, Jacopo Troisi5,6,7,8, Giovanni Scala5,6, Rosario Salvi9, Aldo Pinto1,2 and Rosalinda Sorrentino1,2

1 Department of Pharmacy, DIFARMA, University of Salerno, Fisciano, Salerno, Italy

2 ImmunePharma S.r.l., Salerno, Italy

3 Department of Clinical and Surgical Medicine, University of Naples Federico II, Naples, Italy

4 Anatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”, Naples, Italy

5 Hosmotic Srl, Vico Equense, Naples, Italy

6 Theoreo Srl, Pugliano, Salerno, Italy

7 Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, Baronissi, Salerno, Italy

8 European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy

9 Thoracic Surgery Unit, Ospedale dei Colli, AORN, “Monaldi”, Naples, Italy

* These authors contributed equally to this work

Correspondence to:

Rosalinda Sorrentino,email: [email protected]

Keywords: NSCLC; metabolomic; lipidomic; metabotype; caspase-4

Received: July 09, 2020     Accepted: August 11, 2020     Published: September 22, 2020

Copyright: © 2020 Terlizzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative. We found that circulating caspase-4 was correlated to LDH. However, this effect was not observed in caspase-4 positive tumor tissues, where instead, fatty acid biosynthesis was favoured in that the malonic acid and the palmitic acid were higher than in non-cancerous and caspase-4 negative tissues. The glycolytic pathway in caspase-4 positive NSCLC tissues was bypassed by the malonic acid-dependent lipogenesis. On the other hand, the dysregulated glucose metabolism was regulated by a higher presence of succinate dehydrogenase (SDHA) and by the gluconeogenic valine which favoured Krebs’ cycle.

In conclusion, we found that the recently identified caspase-4 positive subpopulation of NSCLC patients is characterized by a lipidomic profile accompanied by alternative pathways to guarantee glucose metabolism in favour of tumor cell proliferation.


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