Biomarker Research最新文献

Background: While miR-22 is a suppressor of hepatocellular carcinoma (HCC), galectin-1 (Gal-1) serves as a HCC biomarker. Our previous studies have shown the effectiveness of miR-22 gene therapy and silencing Gal-1 as two potential novel options in treating HCC in preclinical mouse models. This study examines the significance of the miR-22-Gal-1 axis in HCC development and treatment.

Methods: The roles of miR-22 and Gal-1 in human HCC were analyzed using the Cancer Genome Atlas database based on their expression levels. The temporal effects of miR-22 were studied by analyzing signaling pathways affected by miR-22 expression levels during HCC progression. AAV8-miR-22, AAV9-Gal-1 siRNA, and LLS30, a Gal-1 inhibitor, were used to treat orthotopic mouse HCC. Spatial transcriptomics established the location-specific effects of miR-22 in mouse HCC. The signaling pathways affected by miR-22 and Gal-1 were identified by analyzing human HCC transcriptomics compared with those found in miR-22, Gal-1 siRNA, or LLS30-treated mouse HCC.

Results: In the early stages of HCC, miR-22-high HCC exhibited extensive upregulation of endobiotic metabolism and xenobiotic detoxification signaling, accompanied by the activation of complement and clotting cascades. In late HCC stages, miR-22-high HCC exhibited heightened innate and adaptive immunity, associated with increased interferon signaling. These impacts were primarily observed in the tumors. At the tumor margin, miR-22 inhibited the Rho GTPase and cell-matrix interaction, revealing its role in reducing matrix remodeling and mobility. In non-tumor areas, miR-22 inhibited inflammation by reducing neutrophil degranulation, platelet activation, chemokine receptor binding, and fiber formation. miR-22, Gal-1 silencing, and LLS30 each exhibited anti-HCC effects and targeted common intracellular signaling pathways. Moreover, the anti-HCC effect of miR-22 was dependent on Gal-1 silencing. miR-22-high/Gal-1-low HCC patients had the best survival outcomes. In addition to the above-mentioned key intracellular pathways, miR-22 gene therapy and Gal-1 siRNA treatment of HCC reduced O-linked glycosylation, suggesting the role of the miR-22-Gal-1 axis in modifying glycosylation, which may affect the extracellular functions of Gal-1.

Conclusion: In summary, the miR-22-Gal-1 axis can be an HCC prognostic biomarker, and it has vital roles in regulating metabolism and tumor immunity.

Classical Hodgkin lymphoma (cHL) is a heterogeneous malignancy with favorable outcomes, but accurate prognostic stratification remains challenging, particularly across all disease stages. Traditional risk models are focused on advanced stages and do not account for tumor microenvironment (TME) dynamics. Soluble cytokines reflecting TME activity may offer additional prognostic value. In our prospective multicenter study, we investigated the prognostic value of pretreatment plasma levels of soluble TARC, sCD30, sCD163, and sIL-6 in 162 newly diagnosed cHL patients and developed a model incorporating these biomarkers for risk prediction across all stages. Cytokine levels were measured using ELISA, and clinical characteristics, treatment responses, and outcomes were collected. The primary endpoint was 5-year progression-free survival (PFS). Elevated levels of sIL-6 and sCD30 were associated with higher disease stage, presence of B-symptoms, extranodal involvement, and inferior 5-year PFS. A novel prognostic model incorporating age, extranodal disease, and high sCD30/sIL-6 levels outperformed IPS-3 in predicting therapy failure. Patients with both elevated sCD30 and sIL-6 levels at diagnosis had significantly worse outcomes. Integrating soluble cytokine biomarkers, particularly sIL-6 and sCD30, into prognostic models enhances risk stratification across all stages of cHL and supports future efforts toward biomarker-driven, personalized treatment strategies.