The incidence of hepatocellular carcinoma (HCC) is high in Taiwan, because Taiwan is one of HBV-endemic areas. Moreover, HCCs are the 2nd most common cause of death caused by malignancies in Taiwan. Early detection of HCC can improve the survival rate because the stage is one of important prognostic factors. Alpha-fetoprotein (AFP) is the most important tumor marker for diagnosis of HCC and surveillance of treatment. However, the sensitivity, the specificity and positive predictive value of AFP are not very satisfactory. The cell cycle inhibitor p27kip1 is known as a potential prognostic marker for HCC. Decreased expression of cell cycle inhibitor p27kip1 is associated with poor prognosis in HCC. The decreased expression of p27kip1 results from increased ubiquitin-proteosome degradation. S-phase kinase associated protein (Skp2) and cyclin-dependent kinase subunit 1 (Cks1) are the subunits of the ubiquitin ligases responsible for the ubiquitin-proteosome degradation of p27kip1. The increased expression of Skp2 and Cks1 were found in many kinds of human cancers. However, there is no report about the relationship between Cks1, Skp2 and p27kip1 expression in hepatocellular carcinoma. In the present study, we investigated the expression of Cks1, Skp2 and p27kip1 and their prognostic roles in hepatocellular carcinoma.
We used highly specific antibodies in immunohistochemistry to examine the expressions of Cks1, Skp2, and p27kip1 on paraffin-embedded tissue section from 75 patients with hepatocellular carcinoma. Meanwhile, we also analyzed the clinical significance of these three proteins with the various clinicopathological factors and follow-up data.
Well-differentiated HCCs tended to express higher level of p27kip1 (55.6%), and lower levels of Skp2 (66.7%) and Cks1 (77.8%). Poorly differentiated HCCs tended to express lower level of p27kip1 (64.3%). The expression of Cks1 was significantly associated with the expression of Skp2 (P=0.000). In contrast, there were no inverse relationships between the expression of p27kip1 and the expressions of Skp2 and Cks1 in the present study. The expressions of p27kip1, Skp2, and Cks1 were significantly associated with disease stage (AJCC TNM stage system and CLIP scoring system). Moreover, there were significant associations between overall survival rates and the expressions of Skp2 and Cks1 (P = 0.036 and 0.015, respectively). Patients with higher expression of Skp2 and Cks1 had worse survival rates.
This is the first report of the expression and prognostic role of Cks1 in HCC. Higher expression of Skp2 and Cks1 were significantly associated with advanced stage and poor prognosis. Thus, both Skp2 and Cks1 may be considered as potential novel prognostic markers providing more accurate prediction of prognosis combined with AFP and therapeutic targets in HCCs.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0815107-152332 |
| Date | 15 August 2007 |
| Creators | Huang, Chinh-wen |
| Contributors | Hsuan-ying Huang, none, Yow-ling Shiue, Chen-Guo Ker |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0815107-152332 |
| Rights | withheld, Copyright information available at source archive |
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