Journal
ONCOLOGY LETTERS
Volume 13, Issue 5, Pages 3395-3402Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2017.5934
Keywords
hepatocellular carcinoma; insulin-like growth factor binding protein-3; insulin-like growth factor; immunohistochemistry
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Funding
- National Nature Science Foundation of China [81225018, 81172340, 30901769]
- 973 Project of China [2010CB912802, 2010CB529404]
- Ph.D. Programs Foundation of The Ministry of Education of China [20110171110078]
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Insulin-like growth factor binding protein-3 (IGFBP-3) has previously been identified as a putative tumor suppressor gene. The present study investigated the clinical and prognostic significance of IGFBP-3 expression levels in patients with hepatocellular carcinoma (HCC). Immunohistochemistry (IHC) probing for IGFBP-3 was performed on paraffin-embedded tissue samples obtained from 120 patients with HCC, including tissue samples from 120 primary cancer sites and 50 matched adjacent non-malignant sites. Receiver-operator curve (ROC) analysis was used to determine the cut-off scores for the presence of IGFBP-3-positive tumor cells and to estimate the survival time of the patients. The threshold for marking the positive expression of IGFBP-3 was 65%, based on the area under the ROC. Positive expression of IGFBP-3 was observed in 65120 (54.2%) of the HCC tissues, and in 36/50 (72%) of the adjacent non-malignant liver tissues. Low levels of IGFBP-3 expression were correlated with tumor size (P=0.003), tumor multiplicity (P=0.044), node (P=0.008), metastasis (P=0.001) and clinical stage (P=0.001), as well as reduced survival time (P=0.015). Using univariate survival analysis, a significant direct correlation between high and low IGFBP-3 expression levels, and patient survival time (mean survival time high IGFBP-3, 39.4 vs. low IGFBP-3, 18.7 months) was identified. Kaplan-Meier analysis demonstrated that IGFBP-3 expressionlevels and patients survival time were significantly correlated (P<0.001). Multivariate analysis revealed IGFBP-3 expression to he an independent parameter (P=0.003). Therefore, low levels of IGFBP-3 expression arc associated with advance clinicopathological classification and may be a predictor of poor survival in patients with HCC. Furthermore, these findings suggest that IGFBP-3 may serve as an independent molecular marker for the evaluation of prognosis in patients with HCC.
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