TIMP-3 Expression Associates with Malignant Behaviors and Predicts Favorable Survival in HCC

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.