胆囊癌中PTEN的表观遗传下调
Epigenetic Downregulation of PTEN in Gallbladder Cancer.
作者信息
Tekcham Dinesh Singh, Gupta Sanjeev, Shrivastav Braj Raj, Tiwari Pramod Kumar
机构信息
Centre for Genomics, Molecular and Human Genetics, Jiwaji University, Gwalior, Madhya Pradesh, 474 011, India.
School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, 474 011, India.
出版信息
J Gastrointest Cancer. 2017 Mar;48(1):110-116. doi: 10.1007/s12029-017-9919-8.
PURPOSE
Gallbladder cancer (GBC) is becoming a global health problem. Phosphatase and tensin homolog (PTEN), also known as guardian gene of cancer, encodes a protein, which dephosphorylates phosphatidylinositol (3,4,5) triphosphate {PtdIns (3,4,5) P3 } into phosphatidylinositol (4,5) diphosphate {PtdIns (4,5) P2} that results in the inhibition of AKT/PKB signaling pathway. PTEN plays a key role in the pathogenesis of various cancers. However, its role in GBC is still obscure. The present study was aimed to identify the epigenetic role of PTEN in GBC and GSD.
METHODS
PTEN promoter methylation was studied by methylation-specific PCR in 50 GBC and 30 GSD tissues. Transcript level expression of PTEN was analyzed by reverse transcriptase PCR and quantitative PCR in 20 GBC and 20 GSD tissue samples. Immunohistochemistry was performed on tissue microarrays of 136 GBC samples to correlate the methylation pattern with the pattern of in situ expression of PTEN protein. Student's t test was performed to test the significant level of difference between case and control samples. Values showing p ≤ 0.05 were considered significant.
RESULTS
MS PCR showed PTEN promoter methylation in 30% (15/50) GBC (p = 0.0486) and 22.86% (8/30) GSD (p = 0.0530) cases. RT-PCR and qPCR revealed downregulation of PTEN in advanced GBC cases (p < 0.0001), but, not in GSD (p = 0.901). Immunohistochemistry of GBC tissue microarray scored 1+ in 20.29% (p = 0.0028) and zero or negative in 50% (p < 0.0001) GBC cores.
CONCLUSIONS
Thus, PTEN may be considered as a useful biomarker for the management of GBC, however, needs larger sample size to validate it further.
目的
胆囊癌（GBC）正成为一个全球性的健康问题。磷酸酶和张力蛋白同源物（PTEN），也被称为癌症的守护基因，编码一种蛋白质，该蛋白质将磷脂酰肌醇（3,4,5）三磷酸{PtdIns(3,4,5)P3}去磷酸化为磷脂酰肌醇（4,5）二磷酸{PtdIns(4,5)P2}，从而导致AKT/PKB信号通路的抑制。PTEN在各种癌症的发病机制中起关键作用。然而，其在胆囊癌中的作用仍不清楚。本研究旨在确定PTEN在胆囊癌和胆囊息肉样病变（GSD）中的表观遗传作用。
方法
通过甲基化特异性PCR研究50例胆囊癌组织和30例胆囊息肉样病变组织中PTEN启动子甲基化情况。通过逆转录PCR和定量PCR分析20例胆囊癌组织样本和20例胆囊息肉样病变组织样本中PTEN的转录水平表达。对136例胆囊癌样本的组织芯片进行免疫组织化学分析，以将甲基化模式与PTEN蛋白的原位表达模式相关联。采用学生t检验来检验病例组和对照组样本之间差异的显著水平。p≤0.05的值被认为具有显著性。
结果
甲基化特异性PCR显示，30%（15/50）的胆囊癌病例（p = 0.0486）和22.86%（8/30）的胆囊息肉样病变病例（p = 0.0530）存在PTEN启动子甲基化。逆转录PCR和定量PCR显示，晚期胆囊癌病例中PTEN表达下调（p < 0.0001），但在胆囊息肉样病变中未下调（p = 0.901）。胆囊癌组织芯片的免疫组织化学分析显示，20.29%的胆囊癌核心评分为1+（p = 0.0028），50%评分为零或阴性（p < 0.0001）。
结论
因此，PTEN可被视为胆囊癌管理的一个有用生物标志物，然而，需要更大样本量来进一步验证。
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