The tissue inhibitors of metalloproteinases (TIMPs) are proteins that specifically inhibit the proteolytic activity of the matrix metalloproteinases (MMPs). TIMP-3, the only member of the TIMPs that can tightly bind to the extracellular matrix, has been identified as a unique tumor suppressor that demonstrates the ability to inhibit tumor angiogenesis, invasion, and metastasis. This study aimed to detect the expression of TIMP-3 in hepatocellular carcinoma (HCC) and investigate the association between TIMP-3 expression and its clinicopathological significance in HCC patients. In the current study, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting of HCC cell lines and one-step quantitative reverse transcription PCR (qPCR) and immunohistochemistry (IHC) analyses in HCC tissues were performed, to characterize the TIMP-3 expression. Kaplan-Meier survival and Cox regression analyses were utilized to evaluate the prognosis of 101 HCC patients. The results showed that the expression of TIMP-3 in HCC was significantly decreased relative to that of non-cancerous cells and tissues. Furthermore, the TIMP-3 expression was statistically associated with malignant behaviors of HCC, including portal vein invasion (p = 0.036) and lymph node metastasis (p = 0.030). Cox regression analysis revealed that TIMP-3 expression was an independent prognostic factor for disease-free survival (p = 0.039) and overall survival (p = 0.049). These data indicate that TIMP-3 expression is a valuable prognostic biomarker for HCC and that TIMP-3 expression suggests a favorable prognosis for HCC patients.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149530 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106161 | PLOS |
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