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  • 1
    In: The International Journal of Biological Markers, SAGE Publications, Vol. 24, No. 3 ( 2009-07), p. 210-210
    Abstract: Survivin, also known as BIRC5, is the smallest member of the mammalian IAP family and is a well recognized inhibitor of apoptosis with an important role in cell-cycle regulation. It is detected in fetal and neoplastic adult tissue, but not in normal tissues. Survivin acts on cancer promotion not only by the inhibition of apoptosis but also by acceleration of the proliferative activity of cancer cells and several papers have suggested the involvement of this protein in hepatocarcino-genesis. It has been reported that the detection of HCC biomarkers circulating as IgM immune complexes (ICs) improved the diagnosis and prognosis of HCC. The aim of this study was to compare the expression of survivin as an IgM immune complex in serum from healthy controls and of patients with cirrhosis and patients with HCC to identify a novel biomarker for the monitoring of liver diseases. Methods Serum levels of survivin-IgM from 1 97 individuals, including 39 healthy subjects, 94 patients with cirrhosis and 64 with HCC, were measured by ELISA and the relationship with clinical parameters was evaluated. Results Survivin-IgM was almost undetectable in sera from healthy subjects, high in patients with cirrhosis, and moderately lower in patients with HCC. The survivin-IgM assay was positive in 62 of 94 patients with cirrhosis (66%) and in 28 of 64 patients with HCC (43.7%) using a cut-off of 264.89 AU/mL (specificity of 94%). Statistical analysis showed that IC values were significantly different between groups (cirrhosis versus healthy control group, p 〈 0.001; HCC versus cirrhosis group, p 〈 0.001). Circulating survivin-IgM ICs in patients with HCC were lower than in patients with cirrhosis; in fact, the statistical significance in comparison with healthy subjects was lost. On the other hand, the concentration of circulating survivin-IgM ICs was found to increase with progression of Child score. Conclusions The high expression of survivin-IgM in sera from patients with cirrhosis and the values of sensitivity indicate that survivin-IgM could be a novel candidate biomarker for cirrhotic disease. Furthermore, the increase in ICs with the progression of Child score seems to promote the survivin-IgM immune complex as marker of liver failure. Survivin-IgM was found to be lower in sera from HCC patients. Follow-up studies are in progress to monitor patients with cirrhosis and to validate the association of the downregulation of this marker with progression towards hepatocellular carcinoma.
    Type of Medium: Online Resource
    ISSN: 1724-6008 , 1724-6008
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 1475778-3
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  • 2
    In: The International Journal of Biological Markers, SAGE Publications, Vol. 24, No. 3 ( 2009-07), p. 206-206
    Abstract: Biomarkers for early hepatocellular carcinoma (HCC) detection are still a clinical need. Recent data indicate that cancer-associated antigens lead to the formation of circulating IgM-linked immune complexes as the result of natural IgM production by the innate immune response. The SCCA-IgM immune complex has already been described for primary liver cancer detection. Osteopontin (OPN) is a member of the SIBLING family of proteins recently shown to be related to tumorigenesis, progression and metastasis in various cancer types. Aim To evaluate the serum levels of the OPN-IgM complex in comparison to the SCCA-IgM complex in patients with HCC. Patients A total of 256 patients were analyzed including 151 patients with HCC (M/F 115/36; mean age ± SD: 67 ± 12 years) and 106 patients with cirrhosis (M/F 68/38; mean age ± SD: 62 ± 12 years). HCC, tested before any therapeutic approach, was mainly of viral etiology (58% HCV, 11% HBV), while alcohol abuse (22%) was the main risk factor for the remaining cases. A similar distribution was found in patients with cirrhosis (46% HCV, 15% HBV, 38% alcohol). Methods Serum levels of OPN-IgM were measured using a homemade ELISA assay with a polyclonal anti-human OPN antibody (Biodesign Int, USA). SCCA-IgM was detected in serum using an ELISA assay kit (Hepa-IC, Xeptagen). Results OPN-IgM was positive in 64/151 (42%) patients with HCC and in 45/106 (42%) patients with cirrhosis (specificity 58%), while the reference biomarker SCCA-IgM showed 35% sensitivity (49/139) and 71 % specificity. When patients were stratified on the basis of etiology, the sensitivity values for OPN-IgM and SCCA-IgM were 51% vs 44% in HCV patients, and 36% vs 23% in the other patients, while the specificity was lower for OPN-IgM (55% vs 69% in HCV patients; 62% vs 72% in the other patients). Combination of the two biomarkers resulted in an increase in sensitivity to 63% for viral etiology and to 40% for nonviral etiology. Conclusion Different IgM-linked biomarkers are detectable in primary liver cancer. OPN-IgM and SCCA-IgM showed a similar behavior, while the combination of these biomarkers increased the diagnostic performance for primary liver cancer.
    Type of Medium: Online Resource
    ISSN: 1724-6008 , 1724-6008
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 1475778-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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