Abstract
BackgroundThe 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.MethodsMethylation 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.ResultsAnalysis 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.ConclusionMethylation 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.
Highlights
The secreted protein acidic and rich in cysteine (SPARC) plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration
Methylation of the SPARC gene transcriptional regulation region (TRR) in pancreatic tissues and pancreatic cancer cells According to the NCBI genome database, we analyzed the SPARC gene TRR and found a CpG island around the transcriptional start site between the upstream -29 bp and downstream +191 bp using the methylation analysis software of Methyl Primer Express v1.0 (ABI)
CpG Region 2 was rarely methylated in real normal pancreatic tissues but CpG Region 1 was more frequently methylated in some of normal tissues
Summary
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. It is clear that many genetic and epigenetic alterations occur during pancreatic tumorigenesis [5] Among these alterations, methylation of the tumor suppressor gene promoter results in gene silencing [6], which may take place during the very early stages of pancreatic cancer development. Methylation of the tumor suppressor gene promoter results in gene silencing [6], which may take place during the very early stages of pancreatic cancer development Detection of such aberrant DNA methylation of tumor suppressor genes could be used as a diagnostic marker for pancreatic cancer [7]. Defining altered gene expression and understanding the underlying molecular mechanism in pancreatic cancer are urgently needed
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