Published online Dec 14, 2019. doi: 10.3748/wjg.v25.i46.6713
Peer-review started: August 13, 2019
First decision: September 10, 2019
Revised: September 28, 2019
Accepted: October 22, 2019
Article in press: October 22, 2019
Published online: December 14, 2019
A large body of evidence has now confirmed that secreted protein acidic and rich in cysteine (SPARC) gene plays an inhibitory role in a variety of tumors, including ovarian cancer, pancreatic cancer, and colon cancer. In addition, the SPARC gene also plays an important role in anti-angiogenesis, the inhibition of cell proliferation, and cell cycle arrest. However, little is known about the precise role of SPARC in gastric cancer (GC). In the present research, we conducted a conjoint analysis of the correlation between methylation, gene expression, and patient prognosis in GC cells and tissues.
SPARC is considered to represent a potential therapeutic target and biomarker of GC. Therefore, the identification and analysis of aberrant methylation of the SPARC gene, and its significance in GC, is of significant interest.
In this study, we aimed to investigate the expression levels of the SPARC gene in different GC cell lines and tissues and investigated how these factors were related to clinicopathological features. Further studies analyzed the correlation between methylation, gene expression, and patient prognosis. We also demonstrated potential effects on biological function.
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of SPARC in a normal gastric mucous membrane cell line, four GC cell lines, and 66 matched samples. We also used methylated-specific PCR to detect the SPARC gene promoter region and investigated the correlation between methylation and clinicopathological features. We also investigated the effects of the demethylation drug, 5-azacytidine, and the acetylated inhibitor, trichostatin A (TSA), on BGC-823 cells. By constructing a stable cell line that over-expressed SPARC, we were able to explore its effects on biological function using the cell counting kit-8 kit, the scratch method, flow cytometry, and the transwell chamber method.
qRT-PCR results showed that the expression level of SPARC gene in GC tissues and cell lines was significantly lower than controls. We also concluded that low expression levels of SPARC were related to Borrmann type, TNM staging, and lymph node metastasis. The hypermethylation of SPARC was positively correlated with Borrmann type, TNM staging, and lymph node metastasis. We transfected a plasmid vector containing the SPARC gene into BGC-823 cells and analyzed changes in biological function using the cell counting kit-8 kit, scratches, flow cytometry, and Transwell assays. Data showed that the over-expression of SPARC inhibited cell proliferation, migration, and invasion, arrested the cell cycle, and promoted cellular apoptosis.
In conclusion, we provide new and reliable evidence for the role of SPARC in GC. We believe that SPARC may act as an anti-oncogene to inhibit the tumorigenesis of GC. Methylation plays a critical role in regulating SPARC gene expression and is significantly associated with GC. Furthermore, SPARC may represent a potential biomarker and therapeutic target for GC. By analyzing the effects of SPARC gene expression, it may be possible to develop better and more accurate treatment and thus improve the prognosis of patients with GC.
Studying tumor inhibitor gene methylation provides a new strategy and direction for the examination, treatment, and prognosis of GC. Further studies should be conducted to analyze the regulatory mechanisms associated with the SPARC gene and potential links with the occurrence and development of GC.