Chronic diseases are the leading cause of death worldwide, accounting for approximately 71 % of global death each year, with particular high mortality rates in low- and middle-income countries. These diseases have become a significant public health challenge (Bauer et al., 2014, Tang et al., 2019). As one of the most common chronic diseases, cancer is a major global health challenge that severely impacts human health and quality of life. Cardiovascular diseases, chronic respiratory diseases, and metabolic diseases also impose a significant socioeconomic burden and strain on healthcare resources. Their prevalence is closely associated with population aging, urbanization, poor dietary habits, lifestyle and environmental impacts (Anderson and Durstine, 2019, Shang et al., 2023). Early diagnosis and effective treatment are crucial for improving prognosis and alleviating the burden of chronic diseases (Shlipak et al., 2021).

Current diagnostic and therapeutic approaches for chronic diseases like cancer primarily rely on clinical assessments, imaging technique and laboratory examination, which are often invasive, costly, time-consuming and lacking specificity (Reynolds et al., 2018). Consequently, the study focusing on identifying novel and non-invasive biomarkers has become the key to improving early diagnosis and personalized treatment strategies. Circulating biomarkers are considered as promising biomarkers for early diagnosis of disease due to their stability in body fluids, as well as their sensitivity and specificity in monitoring disease onset and progression.

Circulating biomarkers refer to the molecules present in body fluids such as blood, urine and cerebrospinal fluid, which reflect the occurrence, development, and pathological process of diseases. These biomarkers can be categorized into nucleic acids, proteins and metabolites. Nucleic acid biomarkers, including circulating free DNA (cfDNA) and non-coding RNA (ncRNA), play roles in detecting tumor-specific mutations and monitoring response to therapy (Goh et al., 2023, Marcuello et al., 2019, van’t Erve et al., 2024). High-throughput sequencing (NGS), digital PCR (dPCR) and real-time fluorescence quantitative PCR (qPCR) are commonly used for detection. Circulating protein biomarkers monitor disease status by detecting changes in specific proteins, particularly in cancer therapy. Enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) are commonly employed for protein detection. Metabolic biomarkers reflect the physiological state through metabolic products and provide information for tumor metabolism and progression. Detection methods for metabolic biomarkers typically include liquid-/gas- chromatography-mass spectrometry (LC-MS/MS, GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. The comprehensive investigation of these biomarkers has yielded novel insights into the mechanisms underlying cancer initiation and progression, with significant implications for cancer diagnosis, treatment, and prognostic evaluation. Furthermore, these biomarkers demonstrate comparable potential in the pathophysiological processes of other prevalent chronic diseases. The joint study of them had provided novel insights into the biology of human metabolism and disease pathogenesis (Karjalainen et al., 2024). As shown in Fig. 1, environmental exposures reflect changes in the internal physiological state of the organism by causing changes in circulating markers, which are thus closely related to the onset, progression and prognosis of disease. Circulating biomarker identification through liquid biopsy has garnered significant attention due to its advantages of simple sampling, minimal invasiveness, and high repeatability. This approach holds great promise for early screening, prognosis assessment, targeted therapy selection, and monitoring drug resistance in chronic diseases (Alix-Panabières and Pantel, 2021, Butz et al., 2024, Duffy and Crown, 2022, Wang et al., 2021).

In recent years, research on circulating biomarkers has rapidly advanced, with a growing focus on multi-omics integration, highly sensitive detection methods and the translation of these innovations to clinical applications. For example, the combined analysis of circulating tumor DNA (ctDNA), proteins and metabolites had been shown to improve disease diagnostic accuracy by integrating multi-omics data (Zhou et al., 2024). Additionally, techniques such as single-molecule sequencing and dPCR enable the precise detection of low-abundance nucleic acid mutations, facilitating the discovery of new disease-specific biomarkers (Motone et al., 2023). Meanwhile, detection technologies are rapidly developing towards high-throughput, multimodal, real-time, and intelligent platforms. For example, microfluidic chips and nanopore technology enabled rapid detection, significantly reducing the time required for analysis (Liu et al., 2022); while miniaturized devices were increasingly capable of enriching, measuring, and analyzing specific circulating biomarkers (Natalia et al., 2023a). Technological advances provide support for biomarker discovery and validation, and the integration of multimodal analyses with AI-driven diagnostic platforms holds significant promise for enhancing the application in precision medicine.

Circulating biomarkers reflect both health status and environmental exposures. Recent studies show that long non-coding RNAs (lncRNAs) mediate the effects of environmental factors, such as ozone and PM2.5 on human health, influencing circulating biomarkers of inflammation (Diao et al., 2023, Fang et al., 2024), microRNAs (miRNAs) can be used as early warning biomarkers in polycyclic aromatic hydrocarbons(PAH)-exposed population (Rani et al., 2021), and the intricate interplay between environmental pollutants and exosomes shed light on a novel paradigm in environmental health and disease (Javdani-Mallak & Salahshoori, 2024).

In conclusion, circulating biomarkers have great potential in the diagnosis and treatment of cancer and other chronic diseases. With the development of technology, more accurate, rapid, cost-effective and non-invasive circulating biomarkers will be applied in the early detection, prognosis assessment and personalized treatment of chronic diseases. The comprehensive study of these biomarkers not only revealed the health status or the progression of diseases but also indicated environmental exposure factors, improving the quality of life of patients and effectively reducing the global burden of chronic diseases.