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DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling.

Liu Y, Zhou R, Yuan X, Han N, Zhou S, Xu H, Guo M, Yu S, Zhang C, Yin T, Wu K - Oncotarget (2015)

Bottom Line: In this study, we employed public microarray data analysis and tissue microarrays (TMAs) technologies and showed that DACH1 expression was reduced in HCC even at early stage and associated with the tumor progression.In agreement, the abundance of DACH1 was inversely correlated with several Wnt target genes.Collectively, our study indicated β-catenin is a novel target of DACH1 in HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

ABSTRACT
The cell fate determination factor Dachshund (DACH1) functions as a novel suppressor in the progression of various neoplasms. Previous study has suggested that hypermethylation of promoter region was responsible for the reduction of DACH1 expression in hepatocellular carcinoma (HCC), and associated with the progression of HCC, but the clinical significance and the exact molecular mechanisms of DACH1 in the progression of HCC remain unclear. In this study, we employed public microarray data analysis and tissue microarrays (TMAs) technologies and showed that DACH1 expression was reduced in HCC even at early stage and associated with the tumor progression. Notably, Kaplan-Meier analysis further indicated DACH1 could be an independent prognostic factor for the overall survival of HCC. Further, mechanistic studies revealed that overexpression of DACH1 inhibited the growth and migration of HCC cell line, which were dependent in part on the inactivation of Wnt pathway via phosphorylation of GSK3β to suppress β-catenin. In agreement, the abundance of DACH1 was inversely correlated with several Wnt target genes. Collectively, our study indicated β-catenin is a novel target of DACH1 in HCC.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry analysis of DACH1 and cyclin D1 on HCC tissuesIn consecutive TMA slides, the representative HE staining and immunohistochemistry images presented for DACH1 and cyclin D1.
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Figure 2: Immunohistochemistry analysis of DACH1 and cyclin D1 on HCC tissuesIn consecutive TMA slides, the representative HE staining and immunohistochemistry images presented for DACH1 and cyclin D1.

Mentions: To further explore the role of DACH1 in HCC development, we employed a larger series of HCC patients. The microarray included more HCC patients with various tumor grades and stages (n = 95) and additional control groups (e. g., benign inflammation and normal tissue). DACH1 expression in tumor tissues was arbitrarily classified as high (IHC score ≥ 6) in 48 cases and low (IHC score < 6) in 47 HCC patients. We also investigated the expression of cyclin D1, because it is a crucial proliferate hallmark of multiple cancers and previous reports confirmed cyclin D1 gene was a functional target of DACH1 [11, 20, 21]. Immunohistochemical staining confirmed that DACH1expression was low in cholangiocarcinoma and primary HCC (Fig. 2). Intriguingly, expression of DACH1 was strongly correlated with the tumor progression. In the low DACH1 group, the expression level of cyclin D1 was significantly higher than it in the high group (Fig. 2). In comparison with the clinicopathological parameters between groups, including age, sex, tumor grading, TNM staging as well as the expression of cyclin D1, we found the level of DACH1 expression was significantly associated with tumor grade (χ2 test, p < 0.001) and illustrated a reverse coordination with cyclin D1 (χ2 test, p = 0.048), whereas age, sex and TNM staging showed no-statistical significance with DACH1 (Table 1).


DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling.

Liu Y, Zhou R, Yuan X, Han N, Zhou S, Xu H, Guo M, Yu S, Zhang C, Yin T, Wu K - Oncotarget (2015)

Immunohistochemistry analysis of DACH1 and cyclin D1 on HCC tissuesIn consecutive TMA slides, the representative HE staining and immunohistochemistry images presented for DACH1 and cyclin D1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496171&req=5

Figure 2: Immunohistochemistry analysis of DACH1 and cyclin D1 on HCC tissuesIn consecutive TMA slides, the representative HE staining and immunohistochemistry images presented for DACH1 and cyclin D1.
Mentions: To further explore the role of DACH1 in HCC development, we employed a larger series of HCC patients. The microarray included more HCC patients with various tumor grades and stages (n = 95) and additional control groups (e. g., benign inflammation and normal tissue). DACH1 expression in tumor tissues was arbitrarily classified as high (IHC score ≥ 6) in 48 cases and low (IHC score < 6) in 47 HCC patients. We also investigated the expression of cyclin D1, because it is a crucial proliferate hallmark of multiple cancers and previous reports confirmed cyclin D1 gene was a functional target of DACH1 [11, 20, 21]. Immunohistochemical staining confirmed that DACH1expression was low in cholangiocarcinoma and primary HCC (Fig. 2). Intriguingly, expression of DACH1 was strongly correlated with the tumor progression. In the low DACH1 group, the expression level of cyclin D1 was significantly higher than it in the high group (Fig. 2). In comparison with the clinicopathological parameters between groups, including age, sex, tumor grading, TNM staging as well as the expression of cyclin D1, we found the level of DACH1 expression was significantly associated with tumor grade (χ2 test, p < 0.001) and illustrated a reverse coordination with cyclin D1 (χ2 test, p = 0.048), whereas age, sex and TNM staging showed no-statistical significance with DACH1 (Table 1).

Bottom Line: In this study, we employed public microarray data analysis and tissue microarrays (TMAs) technologies and showed that DACH1 expression was reduced in HCC even at early stage and associated with the tumor progression.In agreement, the abundance of DACH1 was inversely correlated with several Wnt target genes.Collectively, our study indicated β-catenin is a novel target of DACH1 in HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

ABSTRACT
The cell fate determination factor Dachshund (DACH1) functions as a novel suppressor in the progression of various neoplasms. Previous study has suggested that hypermethylation of promoter region was responsible for the reduction of DACH1 expression in hepatocellular carcinoma (HCC), and associated with the progression of HCC, but the clinical significance and the exact molecular mechanisms of DACH1 in the progression of HCC remain unclear. In this study, we employed public microarray data analysis and tissue microarrays (TMAs) technologies and showed that DACH1 expression was reduced in HCC even at early stage and associated with the tumor progression. Notably, Kaplan-Meier analysis further indicated DACH1 could be an independent prognostic factor for the overall survival of HCC. Further, mechanistic studies revealed that overexpression of DACH1 inhibited the growth and migration of HCC cell line, which were dependent in part on the inactivation of Wnt pathway via phosphorylation of GSK3β to suppress β-catenin. In agreement, the abundance of DACH1 was inversely correlated with several Wnt target genes. Collectively, our study indicated β-catenin is a novel target of DACH1 in HCC.

No MeSH data available.


Related in: MedlinePlus