title: TIMP-3 expression associates with malignant behaviors and predicts favorable survival in HCC.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Maoying
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Ni
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Pathology, Jiangsu Province Geriatric Institute, Nanjing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Jiangsu Province Geriatric Institute, Nanjing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Hematology and Oncology, Jiangsu Provincial Hospital, Nanjing, China.
authors.forename: Jiaren
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China; Huadong Medical Institute of Biotechniques, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*
chemical_list: C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3