Peripheral Blood Biomarkers in Non-Hodgkin Lymphoma: Evaluation of Classical Serological Markers and Emerging Liquid Biopsy Approaches

Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of lymphoid malignancies with varied clinical behavior, treatment response, and prognosis. While tissue biopsy remains the diagnostic gold standard, peripheral blood biomarkers have gained increasing importance as minimally invasive, cost-effective tools for diagnosis, prognostic stratification, treatment monitoring, and detection of minimal residual disease. Classical serological biomarkers such as lactate dehydrogenase (LDH), beta-2 microglobulin (β2-microglobulin), and carcinoembryonic antigen (CEA) are widely available and routinely used in clinical practice, particularly in resource-limited settings. Recent advances have further expanded the scope of peripheral blood biomarkers through liquid biopsy approaches, including circulating tumor DNA (ctDNA), circulating RNAs, and epigenetic markers. This review provides a comprehensive and simplified synthesis of global evidence on peripheral blood biomarkers in NHL, with particular emphasis on the evaluation of serum LDH, β2-microglobulin, and CEA, their biological basis, clinical utility, prognostic significance, and public health relevance, while also highlighting emerging molecular approaches and future directions.