Godzien Joanna, Lopez-Lopez Angeles, Sieminska Julia, Jablonowski Kacper, Pietrowska Karolina, Kisluk Joanna, Mojsak Malgorzata, Dzieciol-Anikiej Zofia, Barbas Coral, Reszec Joanna, Kozlowski Miroslaw, Moniuszko Marcin, Kretowski Adam, Niklinski Jacek, Ciborowski Michal
Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Spain.
Front Mol Biosci. 2024 Jan 15;10:1279645. doi: 10.3389/fmolb.2023.1279645. eCollection 2023.
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. 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. 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. 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.
肺癌是研究最为频繁的癌症类型之一，也是最常见且致命的肿瘤。我们之前对非小细胞肺癌（NSCLC）的研究揭示了癌症患者体内深度的脂质谱重编程和氧化还原状态破坏。肺细胞膜富含易被氧化的磷脂，导致生物活性氧化磷脂酰胆碱（oxPCs）的形成。研究表明，持续升高的oxPCs水平会引发慢性炎症，从而产生有害影响。然而，最近的报告显示某些oxPCs具有抗炎、促生存和保护内皮屏障的特性。因此，我们旨在测量NSCLC患者体内oxPCs的水平，并研究它们在肺癌中的潜在作用。为了探究肺癌中的oxPCs谱，我们对来自200例NSCLC患者（包括腺癌（ADC）和鳞状细胞癌（SCC）这两种最常见的NSCLC亚型）以及慢性阻塞性肺疾病（COPD）患者作为对照组的近350份血浆和肺组织样本进行了深入的多层次代谢组学分析。首先，我们对血浆样本进行了oxPC分析。其次，我们分析了在NSCLC肿瘤手术切除过程中采集的肿瘤和非癌性肺组织。由于肿瘤组织的异质性，后续分析涵盖了周围健康组织以及外周和中央肿瘤。为了评估患者中观察到的表型变化是否与测得的oxPC水平相关，代谢组学数据与病历数据相结合。我们观察到NSCLC患者血浆样本中长链oxPCs占主导，组织样本中短链oxPCs占主导。在中央肿瘤区域观察到oxPCs的浓度最高。与对照组相比，ADC患者的oxPCs水平高于SCC患者。与短链oxPCs积累相关的有害影响表明，这些分子可能具有更大的治疗效用而非诊断价值，特别是考虑到oxPCs水平升高是多种癌症的一个标志。
