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Published on: September 12, 2019
Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study
Xianglian Ding1, Xifang Cheng, Meixia Gong
1From the Department of Radiology, The 5th Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Abstract:
Programmed cell death 4 (PDCD4) is a novel tumor suppressor, which is involved in the initiation and progression of cancers. However, the role of PDCD4 in hepatocellular carcinoma (HCC) has not been reported. The aim of this study was to investigate the molecular mechanism and clinical significance of PDCD4 inactivation in HCC.The mRNA levels of PDCD4 in HCC tissues and adjacent nontumor tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Bisulfite sequencing PCR was performed to determine the methylation status of PDCD4 promoter. Furthermore, the mRNA expression level and the methylated level of PDCD4 were analyzed with the clinical and pathological characteristics.qRT-PCR analysis showed that PDCD4 mRNA levels in tumor tissues were significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of PDCD4 promoter was significantly higher in HCC tissues than that in adjacent nontumor tissues. PDCD4 mRNA levels and promoter methylation levels were both statistically correlated with metastasis and the degree of differentiation in HCC. In addition, the correlation between PDCD4 hypermethylation, mRNA levels, and overall survival (OS) was statistically significant.Our results indicated that PDCD4 may be a novel candidate of tumor suppressor gene in HCC, and that promoter hypermethylation is an important mechanism for its downregulation and is also a good predictor of OS for HCC.
Insights
Programmed cell death 4 (PDCD4) is downregulated in hepatocellular carcinoma (HCC) due to promoter hypermethylation. This inactivation serves as a significant predictor of overall survival in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Programmed cell death 4 (PDCD4) is recognized as a tumor suppressor gene implicated in various cancer types.
- The specific role and inactivation mechanisms of PDCD4 in hepatocellular carcinoma (HCC) remain largely uninvestigated.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying PDCD4 inactivation in HCC.
- To assess the clinical significance of PDCD4 alterations as a prognostic marker in HCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure PDCD4 mRNA levels in HCC and adjacent non-tumor tissues.
- Bisulfite sequencing PCR was utilized to evaluate the methylation status of the PDCD4 promoter.
- Correlation analyses were performed between PDCD4 expression/methylation and clinical/pathological characteristics, including overall survival.
Main Results:
- PDCD4 mRNA levels were significantly reduced in HCC tissues compared to adjacent non-tumor tissues.
- A significantly higher rate of PDCD4 promoter hypermethylation was observed in HCC tissues.
- Both decreased PDCD4 mRNA levels and increased promoter methylation correlated with metastasis, poorer differentiation, and reduced overall survival in HCC patients.
Conclusions:
- PDCD4 functions as a tumor suppressor gene in HCC.
- Promoter hypermethylation is a key mechanism for PDCD4 downregulation in HCC.
- PDCD4 hypermethylation serves as a valuable prognostic biomarker for overall survival in HCC.
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