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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2014, Vol. 8 Issue (1) : 24-32
Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies
Lunxiu Qin()
Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
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In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivo investigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

Keywords osteopontin (OPN)      hepatocellular carcinoma      metastasis      prognosis      therapeutic target      biomarker      genetic polymorphism     
Corresponding Author(s): Qin Lunxiu,   
Issue Date: 26 April 2014
 Cite this article:   
Lunxiu Qin. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies[J]. Front Med, 2014, 8(1): 24-32.
Fig.1  OPN is one of the leading genes in the metastasis-related gene expression signature of HCC.
Fig.2  Association between the preoperative serum OPN levels and survival rates of HCC patients. Both the OS (left) and disease-free survival (DFS) (right) rates in patients with high preoperative OPN levels (green lines) were significantly decreased compared with those in low-OPN patients (blue lines).
Fig.3  Dynamic changes in the serum OPN levels after liver resection for HCC. (A) Dynamic change patterns of post-surgery OPN levels in the HCC patients. (B) AFP HCC patients had the same changing pattern of postoperative OPN levels. Note: 1W, 1 week; 1M, 1 month; 2M, 2 months. The OPN levels are shown as mean±SD. Boxes represent the 10th to the 90th quartile.
Fig.4  Association of postsurgery serum OPN with treatment response and tumor recurrence after HCC resection. Each dot represents an individual postsurgery OPN measurement plotted against time from surgery. Three patients (red and green lines) were observed with serially serum OPN levels at tumor relapse and after the second operative resection. The red lines denote the AFP patients, whereas the green line denotes the AFP patients.
Fig.5  Prognostic values of the genotypes and their related haplotypes at OPN promoter locus -443 for HCC patients (Kaplan-Meier analyses of 317 patients). Homozygous Ht3 is associated with the best OS (A) and significantly longer TTR (C) than the other haplotypes. Similarly, homozygous -443C genotypes are associated with longer OS and TTR than heterozygous -443 or homozygous -443T genotypes (B, D).
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