Abstract. Previous studies have shown that S100P contributes to the development of a number of tumors. However, its prognostic significance in colorectal cancer (CRC) has not been demonstrated. This study aimed to confirm the expression of S100P in colorectal cancer as well as the epigenetic mechanism underlying its gene expression, and to demonstrate whether S100P could be used to predict prognosis as a biomarker. We tested the expression of S100P in 96 CRCs and their paired tissue controls, as well as 13 colon cancer cell lines by RT-PCR and western blotting. Expression of the S100P protein and mRNA was significantly higher in cancerous regions compared to that in paired non-cancerous tissues (P=4.59x10 -17 , 0.005 respectively). The expression was significantly correlated with the hypomethylation of the S100P promoter (P=4.92x10 -5 ), which was detected by bisulphite sequencing PCR (BSP) and quantitative methylation-specific real-time PCR (QMSP). In stages I to III, the patients with positive expression of S100P protein showed poorer overall survival compared to those with S100P negative expression, P= 0.031. We also measured the preoperative serum S100P levels by ELISA. The patients with normal serum levels of S100P showed favorable prognosis compared with patients with elevated S100P levels (P=0.008). These data suggest that S100P protein may be a potential novel prognostic biomarker in CRC patients.

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.