Abstract 1779: Serum level of DKK1 as a marker for predicting tumor recurrence of hepatocellular carcinoma

Autor: John Mc Luk, Carmen Km Mak, Ching L. Lai, Joyce Mf Lee, Edmund Kk Tung, Jin J. Li, Ronnie Tp Poon, Irene Oi-Lin Ng
Rok vydání: 2010
Předmět:
Zdroj: Cancer Research. 70:1779-1779
ISSN: 1538-7445
0008-5472
Popis: Dickkopf-1 (DKK1), an inhibitor of Wnt/beta-catenin signaling pathway, is upregulated in various cancers including HCC. However, the clinical significance of serum DKK1 in hepatocellullar carcinoma (HCC) remains to be determined. The objective of this study was to investigate the clinical significance of DKK1 and its prognostic value in predicting survival and tumor recurrence in human HCC. Two independent cohorts with 217 and 100 pairs of tumors and corresponding nontumor livers were employed for microarray analysis and real time-quantitative PCR (qPCR), respectively, to investigate the DKK1 transcript levels in human HCC samples. The serum levels of DKK1 were determined in 50 patients with early HCC, 50 patients with advanced HCC, 50 patients with cirrhosis, 50 hepatitis B virus (HBV) carriers, and 30 HCC patients after liver resection, using sandwich ELISA system. Transcript level of DKK1 in the human HCCs was found to be significantly upregulated as compared with the corresponding nontumorous livers in both microarray (P < 0.001) and qPCR cohorts (P < 0.001). Increased expression of DKK1 was associated with advanced tumor stage (P < 0.001), venous infiltration (P < 0.001), high serum alpha-fetoprotein (AFP) level (P < 0.001). Higher level of DKK1 correlated with both poorer overall survival (P = 0.016) and tumor recurrence (P = 0.014). On the other hand, the serum DKK1 level in the group of HBV carriers without HCC (as control) was not significantly different from that of the cirrhosis group (P = 0.086). In contrast, the serum DKK1 level was significantly higher in patients with early HCC (P < 0.001) and advanced HCC (P < 0.001), as compared with the HBV carrier group. Furthermore, the serum DKK1 level in patients after liver resection was significantly reduced (P < 0.001). Higher serum DKK1 level was associated with tumor recurrence (P = 0.046). To conclude, our data have demonstrated that tissue and serum DKK1 levels were significantly and progressively elevated during HCC formation and progression. DKK1 has prognostic role in predicting overall survival and disease-free survival of HCC patients, and serum DKK1 is a potential biomarker for predicting tumor recurrence. (The study was supported in part by a grant from the NSFC/RGC Joint Research Scheme [N_HKU 716/06] and an RGC Collaborative Research Grant [HKU 1/06C]. IOLN is a Loke Yew Professor in Pathology) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1779.
Databáze: OpenAIRE