Objective: Cytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS. Methods: Serum samples were collected from 143 adult and pediatric patients with CSS and 22 healthy controls. The cohort included patients with various diagnoses of primary and secondary HLH and Kawasaki disease (KD)‐like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead‐based multiplex immunoassay (Luminex assay). Serum levels of interferon alpha (IFN‐α), interleukin‐18 (IL‐18), IL‐6, CXCL9, and soluble tumor necrosis factor receptor II (sTNF‐RII) were measured in 165 participants using enzyme‐linked immunosorbent assay (ELISA). Results: Luminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis‐associated HLH and systemic lupus erythematosus‐associated macrophage activation syndrome (MAS) showed elevated IFN‐α; systemic juvenile idiopathic arthritis–associated and adult‐onset Still's disease–associated MAS, X‐linked inhibitor of apoptosis protein deficiency with HLH, and NLRC4‐associated autoinflammatory disorder exhibited higher IL‐18 levels. Additionally, KD shock syndrome had higher IL‐6 levels than the other groups. CXCL9 was significantly elevated in patients with virus‐associated HLH, familial HLH, malignant lymphoma‐associated HLH, and KD‐MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL‐6 levels. Conclusion: Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds. image

It is now widely believed that tumors originate from normal cells as a result of accumulated genetic/epigenetic changes. These alterations affect the signaling pathways at transcriptional and post-transcriptional level that drive cells into uncontrolled cell division, growth, and migration. Recent advancement of molecular technologies have yielded comprehensive gene expression profiling techniques that have successfully provided candidate diagnostic and prognostic markers in human cancers. Serial Analysis of Gene Expression (SAGE) is a technology to facilitate the measurement of mRNA transcripts of normal and malignant tissues in a non-biased and highly accurate and quantitative manner. SAGE produces a comprehensive gene expression portrait without a priori gene sequence information, leading to the identification of novel transcripts potentially involved in the pathogenesis of human cancer. In this review, we provide a brief outline of SAGE to underscore the advantages of the method relative to the other gene expression profiling approaches in cancer research. We also summarize the progression of recent gene expression profiling studies and discuss the current topics of SAGE analysis in cancer research for the development of novel therapeutic interventions.