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Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma.

Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL, Chen ZN - J. Cell. Mol. Med. (2010)

Bottom Line: Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control.Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter.In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi'an, China.

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Kaplan–Meier recurrence and overall survival estimates based on the methylation status of CD147 promoter for all HCC patients. (A) Kaplan–Meier recurrence curve. (B) Kaplan–Meier overall survival curve.
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fig07: Kaplan–Meier recurrence and overall survival estimates based on the methylation status of CD147 promoter for all HCC patients. (A) Kaplan–Meier recurrence curve. (B) Kaplan–Meier overall survival curve.

Mentions: Associations of CD147 promoter methylation with clinicopathological characters were analysed in 54 HCC patients (Table 2). Our results showed that there was no obvious association between methylation status of CD147 promoter derived from MSP analysis and age, gender, differentiation or tumour size of HCC patients (P= 0.964, P= 1.000, P= 0.798 and P= 0.826, respectively). Methylated CD147 promoter was more frequently observed in HCC patients with low serum level of α-fetoprotein (AFP; <500 ng/ml) than that in patients with high serum level of AFP (≥500 ng/ml) (66.7%versus 33.3%; P < 0.05), while unmethylated CD147 promoter was more commonly observed in HCC patients with high serum level of AFP (≥500 ng/ml) than that in patients with low serum level of AFP (<500 ng/ml) (73.8%versus 26.2%; P < 0.05), indicating a significant association between methylation status of CD147 promoter and serum level of AFP in HCC patients (P= 0.025). Prognosis analysis revealed that, compared with patients with ummethylated CD147 promoter, patients with methylated CD147 promoter exhibited a lower recurrence rate (58.3%versus 88.1%; P= 0.019) and death rate (50%versus 83.3%; P= 0.017) (Table 2). A Kaplan–Meier analysis showed that HCC patients with methylated CD147 promoter had significantly longer median recurrence duration than patients with unmethylated CD147 promoter (12 months versus 4.5 months, P= 0.022, log-rank test) (Fig. 7A), and that HCC patients with methylated CD147 promoter had significantly longer median survival duration than patients with unmethylated CD147 promoter (12 months versus 7.0 months, P= 0.023, log-rank test) (Fig. 7B). These results indicated that hypomethylation of CD147 gene was associated with poor prognosis in HCC patients.


Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma.

Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL, Chen ZN - J. Cell. Mol. Med. (2010)

Kaplan–Meier recurrence and overall survival estimates based on the methylation status of CD147 promoter for all HCC patients. (A) Kaplan–Meier recurrence curve. (B) Kaplan–Meier overall survival curve.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373337&req=5

fig07: Kaplan–Meier recurrence and overall survival estimates based on the methylation status of CD147 promoter for all HCC patients. (A) Kaplan–Meier recurrence curve. (B) Kaplan–Meier overall survival curve.
Mentions: Associations of CD147 promoter methylation with clinicopathological characters were analysed in 54 HCC patients (Table 2). Our results showed that there was no obvious association between methylation status of CD147 promoter derived from MSP analysis and age, gender, differentiation or tumour size of HCC patients (P= 0.964, P= 1.000, P= 0.798 and P= 0.826, respectively). Methylated CD147 promoter was more frequently observed in HCC patients with low serum level of α-fetoprotein (AFP; <500 ng/ml) than that in patients with high serum level of AFP (≥500 ng/ml) (66.7%versus 33.3%; P < 0.05), while unmethylated CD147 promoter was more commonly observed in HCC patients with high serum level of AFP (≥500 ng/ml) than that in patients with low serum level of AFP (<500 ng/ml) (73.8%versus 26.2%; P < 0.05), indicating a significant association between methylation status of CD147 promoter and serum level of AFP in HCC patients (P= 0.025). Prognosis analysis revealed that, compared with patients with ummethylated CD147 promoter, patients with methylated CD147 promoter exhibited a lower recurrence rate (58.3%versus 88.1%; P= 0.019) and death rate (50%versus 83.3%; P= 0.017) (Table 2). A Kaplan–Meier analysis showed that HCC patients with methylated CD147 promoter had significantly longer median recurrence duration than patients with unmethylated CD147 promoter (12 months versus 4.5 months, P= 0.022, log-rank test) (Fig. 7A), and that HCC patients with methylated CD147 promoter had significantly longer median survival duration than patients with unmethylated CD147 promoter (12 months versus 7.0 months, P= 0.023, log-rank test) (Fig. 7B). These results indicated that hypomethylation of CD147 gene was associated with poor prognosis in HCC patients.

Bottom Line: Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control.Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter.In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi'an, China.

Show MeSH
Related in: MedlinePlus