胆囊癌分子发病机制中的表观遗传调控 。 你提供的原文似乎不完整，“Epigenetic regulation of ”后面缺少具体内容。
Epigenetic regulation of in the molecular pathogenesis of gallbladder cancer.
作者信息
Tekcham Dinesh Singh, Poojary Satish S, Bhunia Shushruta, Barbhuiya Mustafa Ahmed, Gupta Sanjeev, Shrivastav Braj Raj, Tiwari Pramod Kumar
机构信息
Centre for Genomics; School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India.
Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
出版信息
Indian J Med Res. 2016 May;143(Supplement):S82-S90. doi: 10.4103/0971-5916.191792.
BACKGROUND & OBJECTIVES: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD.
METHODS
Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues.
RESULTS
Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC ( P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression.
INTERPRETATION & CONCLUSIONS: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.
背景与目的
已有报道称，癌症中存在腺瘤性息肉病 coli（APC）功能丧失的情况。APC 的两个启动子 1A 和 1B 在癌症中也发挥作用。但是，APC 启动子在胆囊癌（GBC）和胆结石疾病（GSD）中的表观遗传作用尚不清楚。我们开展这项研究以确定 APC 在 GBC 和 GSD 中的表观遗传作用。
方法
采用甲基化特异性（MS）-PCR 分析 APC 基因的甲基化情况。通过半定量 PCR、实时 PCR 和免疫组织化学（IHC）研究 GBC、GSD 及相邻正常组织中 APC 基因的表达。
结果
在两个启动子中，发现 APC 1A 启动子在 96%的 GBC 中发生甲基化（P = 0.0155），在 80%的 GSD 中发生甲基化（P = 0.015）。外显子 1 在 GBC 的 II 级（P = 0.002）和 III 级（P = 0.0001）中表达下调，而外显子 2 正常表达。IHC 评分分析显示，34.48%的 GBC 病例为 0 或阴性（P = 0.057），24.14%的病例为 1+（P = 0.005），提示 APC 表达缺失。
解读与结论
目前的研究结果表明，晚期 GBC 中存在 APC 的表观遗传沉默。未来，可能建议将 APC 的甲基化模式及其表达分析用于 GBC 的诊断、预后评估和治疗。
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