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Introduction
Lung cancer (LC) is a highly lethal and widespread malignant disease worldwide [1]. Recent data shows that LC is the second most diagnosed cancer worldwide, with about 2.2 million new cases annually, following breast cancer [2]. Small cell lung cancer (SCLC) and NSCLC are its two main histological subtypes. This type accounts for about 85% of all LC cases [3]. Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma are the most common histological subtypes among them [4]. The most significant risk factor for NSCLC is smoking, which involves exposure to a variety of chemical substances, including polycyclic aromatic hydrocarbons and nitrosamines, which are known to possess potent carcinogenic activity. Besides smoking, factors such as occupational exposure, environmental influences, ionising radiation, chronic pulmonary infections, genetic predisposition, and air pollution also elevate the risk of developing NSCLC [5, 6–7]. In recent years, advancements in medical science have rapidly expanded therapeutic options for NSCLC, notably enhancing targeted therapy and immunotherapy alongside traditional treatments like surgery, chemotherapy, and radiotherapy [8, 9]. In the realm of targeted therapy, a variety of targeted drugs are now available for NSCLC patients with specific genetic mutations, such as EGFR, ALK, and ROS1 [10, 11]. In immunotherapy, PD-1/PD-L1 monoclonal antibodies have significantly advanced first-line treatment for advanced NSCLC, especially in patients without driver gene mutations [12]. Immunotherapeutic drugs like Pembrolizumab and Nivolumab are approved for treating NSCLC [13, 14].
Plasma metabolomics is an essential addition to genomics, transcriptomics, and proteomics. Changes in plasma metabolites are a consequence of alterations in DNA, RNA, and proteins [15, 16]. Analyzing metabolites both qualitatively and quantitatively provides a deeper insight into the organism's functional state and pathophysiological changes. Plasma metabolomics has been widely applied in researching numerous diseases, such as LC [17]. Metabolomic techniques can detect specific changes in plasma metabolites of LC patients. For instance, a study utilizing non-targeted metabolomics identified ten differential metabolites in the plasma of LC patients, which could be employed to construct an early diagnostic model for LC with both sensitivity and specificity exceeding 85%. Additionally, metabolite analysis aids in predicting treatment responses in LC patients [17]. Research on plasma metabolites has revealed correlations between certain metabolites and overall survival in NSCLC patients after initial chemotherapy. Research indicates that plasma metabolites may...