ArticleScientific reports2025
Up-regulation of blood-circulating TIM-4-expressing monocytes and potential diagnostic biomarker sTIM-4 in primary liver cancer.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Elevated serum TIM4 is associated with disease severity and serves as a potential predictive biomarker in chronic hepatitis B.BMC infectious diseases · 2026Article
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Authors and funding
10 authors.
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Abstract
Primary hepatocellular carcinoma (PHC) remains a globally prevalent malignancy, where early diagnosis is critical. Monocytes have been implicated in tumor progression. This study investigated the expression of T cell immunoglobulin and mucin domain-containing protein 4 (TIM-4/TIMD4) in PHC tissues and peripheral blood monocytes, and assessed the clinical relevance of soluble TIM-4 (sTIM-4). Immunohistochemistry and bioinformatics analyses revealed reduced TIM-4 expression in PHC tissues, which correlated with immune cell infiltration. Flow cytometry showed elevated TIM-4 expression in circulating monocytes of PHC patients, predominantly within the intermediate subset (91.7%). sTIM-4 and monocyte TIM-4 levels were positively correlated with alpha-fetoprotein (AFP), alanine aminotransferase (ALT), aspartate aminotransferase(AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and negatively correlated with albumin (ALB). Notably, sTIM-4 levels were significantly higher in patients with a history of hepatitis. Logistic regression indicated that elevated sTIM-4 was associated with a 2.29-fold increased risk of PHC. ROC analysis demonstrated that the combination of sTIM-4 and AFP improved diagnostic accuracy for PHC. In conclusion, TIM-4 is downregulated in PHC tissues but upregulated in circulating intermediate monocytes, suggesting its dual role in tumor immunobiology. The combined measurement of sTIM-4 and AFP enhances diagnostic sensitivity and offers predictive value for PHC risk stratification.
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