Abstract
Gastrointestinal cancer is a prevalent disease with high morbidity and mortality. Tissue factor pathway inhibitor 2 (TFPI2) gene could protect the extracellular matrix of cancer cells from degradation and tumor invasion. The goal of our study was to estimate the diagnostic value of TFPI2 hypermethylation in gastric cancer (GC) and colorectal cancer (CRC). TFPI2 methylation was measured by quantitative methylation-specific polymerase chain reaction (qMSP) method in 114 GC and 80 CRC tissues and their paired non-tumor tissues. Our results showed that TFPI2 methylation was significantly higher in tumor tissues (GC: 29.940% vs. 12.785%, P < 0.001; CRC: 26.930% vs. 5.420%, P < 0.001). The methylation level of TFPI2 in colorectal tumor tissues was significantly higher than that in colorectal normal tissues (26.930% versus 0.002%, P < 0.00001). In GC, TFPI2 hypermethylation yielded an area under the curve (AUC) of 0.762 (95% CI: 0.696–0.828) with a sensitivity of 68% and a specificity of 83%. In CRC, TFPI2 hypermethylation yielded an AUC of 0.759 (95% CI: 0.685–0.834) with a sensitivity of 61% and a specificity of 84%. Similarly, TCGA data also supported TFPI2 hypermethylation was a promising diagnostic marker for GC and CRC. Moreover, the dual-luciferase reporter assay showed TFPI2 fragment could upregulate gene expression (fold change = 5, P = 0.005). Data mining further indicated that TFPI2 expression in CRC cell lines was significantly increased after 5’-AZA-deoxycytidine treatment (fold change > 1.37). In conclusion, TFPI2 hypermethylation might be a promising diagnostic biomarker for GC and CRC.
Highlights
The gastrointestinal tract is one of the most predilection sites of tumorigenesis [1]
We recruited 114 gastric cancer (GC) patients, 80 colorectal cancer (CRC) patients and 22 non-tumor individuals to investigate the role of Tissue factor pathway inhibitor 2 (TFPI2) methylation on the detection of GC and CRC
Our data showed that TFPI2 methylation in tumor tissues was significantly higher than that in paired adjacent tissues [GC: 29.940% (15.472%, 47.295%) versus 12.785% (9.678%, 16.575%), P < 0.001; CRC: 26.930% (8.478%, 63.145%) versus 5.420% (1.345%, 16.638%), P < 0.00001; Figure 2A]
Summary
The gastrointestinal tract is one of the most predilection sites of tumorigenesis [1]. Lacking a gold standard of noninvasive method is considered as the major obstacle to the screening, diagnosis and individualized treatment of GC and CRC. For this purpose, it is urgent to identify suitable biomarkers for the early detection of GC and CRC. The development of GC and CRC is characterized by the dysregulation of genetic, epigenetic, and environmental factors [5, 6]. As a bridge between the genetic and environmental factors, epigenetic modification plays an important role in cancer initiation and progression. DNA methylation has been widely studied in GC and CRC [9,10,11,12]
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