Exploration of oxidized phosphocholine profile in non-small-cell lung cancer

Joanna Godzien; Angeles Lopez-Lopez; Julia Sieminska; Kacper Jablonowski; Karolina Pietrowska; Joanna Kisluk; Malgorzata Mojsak; Zofia Dzieciol-Anikiej; Coral Barbas; Joanna Reszec; Miroslaw Kozlowski; Marcin Moniuszko; Adam Kretowski; Jacek Niklinski; Michal Ciborowski

doi:10.3389/fmolb.2023.1279645

Exploration of oxidized phosphocholine profile in non-small-cell lung cancer

Front Mol Biosci. 2024 Jan 15:10:1279645. doi: 10.3389/fmolb.2023.1279645. eCollection 2023.

Authors

Affiliations

¹ Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
² Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Spain.
³ Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland.
⁴ Independent Laboratory of Molecular Imaging, Medical University of Bialystok, Bialystok, Poland.
⁵ Department of Rehabilitation, Medical University of Bialystok, Bialystok, Poland.
⁶ Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
⁷ Department of Thoracic Surgery, Medical University of Bialystok, Bialystok, Poland.
⁸ Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.

Abstract

Introduction: Lung cancer is one of the most frequently studied types of cancer and represents the most common and lethal neoplasm. Our previous research on non-small cell lung cancer (NSCLC) has revealed deep lipid profile reprogramming and redox status disruption in cancer patients. Lung cell membranes are rich in phospholipids that are susceptible to oxidation, leading to the formation of bioactive oxidized phosphatidylcholines (oxPCs). Persistent and elevated levels of oxPCs have been shown to induce chronic inflammation, leading to detrimental effects. However, recent reports suggest that certain oxPCs possess anti-inflammatory, pro-survival, and endothelial barrier-protective properties. Thus, we aimed to measure the levels of oxPCs in NSCLC patients and investigate their potential role in lung cancer. Methods: To explore the oxPCs profiles in lung cancer, we performed in-depth, multi-level metabolomic analyses of nearly 350 plasma and lung tissue samples from 200 patients with NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), the two most prevalent NSCLC subtypes and COPD patients as a control group. First, we performed oxPC profiling of plasma samples. Second, we analyzed tumor and non-cancerous lung tissues collected during the surgical removal of NSCLC tumors. Because of tumor tissue heterogeneity, subsequent analyses covered the surrounding healthy tissue and peripheral and central tumors. To assess whether the observed phenotypic changes in the patients were associated with measured oxPC levels, metabolomics data were augmented with data from medical records. Results: We observed a predominance of long-chain oxPCs in plasma samples and of short-chain oxPCs in tissue samples from patients with NSCLC. The highest concentration of oxPCs was observed in the central tumor region. ADC patients showed higher levels of oxPCs compared to the control group, than patients with SCC. Conclusion: The detrimental effects associated with the accumulation of short-chain oxPCs suggest that these molecules may have greater therapeutic utility than diagnostic value, especially given that elevated oxPC levels are a hallmark of multiple types of cancer.

Keywords: NSCLC; epilipidomics; lung cancer; oxPC; oxidized phospholipids.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Science Centre in Poland (2014/13/B/NZ5/01256), the National Centre for Research and Development in Poland: “Prevention practices and treatment of civilization diseases’ program, STRATEGMED” (contract no. STRATEGMED2/266484/2/NCBR/2015), the Medical University of Bialystok, the National Research Centre in Poland (61/KNOW-16 and 66/KNOW/16), the statutory funds of the Medical University of Bialystok (SUB/1/DN/21/005/4406), the Spanish Ministry of Science and Innovation PID 2021-122490NB-I00, and the Polish Ministry of Education and Science within the project “Excellence Initiative–Research University.”