Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
J Exp Clin Cancer Res. 2010 Mar 26;29(1):28. doi: 10.1186/1756-9966-29-28.
The secreted protein acidic and rich in cysteine (SPARC) plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration. Detection of SPARC gene methylation may be useful as a tumorigenesis marker for early detection of pancreatic cancer.
Methylation of the SPARC gene transcriptional regulation region (TRR) was detected using bisulfite-specific (BSP) PCR-based sequencing analysis in 40 cases of pancreatic cancer and the adjacent normal tissues, 6 chronic pancreatitis tissues, and 6 normal pancreatic tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed.
Analysis of SPARC gene TRR methylation showed two hypermethylation wave peak regions: CpG Region 1 (CpG site 1-7) and CpG Region 2 (CpG site 8-12). Pancreatic tissues have shown methylation in both regions with gradual increases from normal, chronic pancreatitis, and adjacent normal tissues to cancerous tissues. However, Methylation of CpG Region 2 was more sensitive than CpG Region 1 in pancreatic tumorigenesis. Furthermore, the methylation level of CpG Region 2 was associated with increased tumor size and exposure to the risk factors (tobacco smoke and alcohol consumption) for developing pancreatic cancer.
Methylation of the SPARC gene, specifically CpG Region 2, may be an early event during pancreatic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of pancreatic cancer.
富含半胱氨酸的酸性分泌蛋白（SPARC）在调节细胞-基质相互作用以及肿瘤血管生成、增殖和迁移方面发挥着关键作用。检测 SPARC 基因甲基化可能有助于作为胰腺癌早期检测的肿瘤发生标志物。
采用亚硫酸氢盐特异性（BSP）PCR 测序分析方法检测 40 例胰腺癌及其相邻正常组织、6 例慢性胰腺炎组织和 6 例正常胰腺组织中 SPARC 基因转录调控区（TRR）的甲基化情况。在选定的病例中还进行了 BSP 克隆测序分析。收集并分析了癌症患者的临床病理资料。
对 SPARC 基因 TRR 甲基化的分析显示出两个高甲基化波峰区域：CpG 区域 1（CpG 位点 1-7）和 CpG 区域 2（CpG 位点 8-12）。胰腺组织在两个区域均显示出甲基化，其甲基化程度从正常组织、慢性胰腺炎组织和相邻正常组织逐渐增加到癌组织。然而，CpG 区域 2 的甲基化比 CpG 区域 1 在胰腺肿瘤发生中更为敏感。此外，CpG 区域 2 的甲基化水平与肿瘤大小的增加以及患胰腺癌的危险因素（吸烟和饮酒）暴露有关。
SPARC 基因的甲基化，特别是 CpG 区域 2，可能是胰腺肿瘤发生的早期事件，应进一步作为胰腺癌早期检测的肿瘤发生标志物进行评估。
