Fig 1.
Epigenetic conversion in the p53 pathway.
Table 1.
Distribution of clinical and pathological factors for correlation with gene & methylation status and univariable prognostic analysis in 163 pStageII/III gastric cancer with gastrectomy and subsequent S-1 treatment.
Fig 2.
Kaplan Meier analysis of overall survival (OS) and relapse free survival (RFS) of primary gastric cancer patients with pathological stage II/III (pStage II/III) who underwent curative resection and postoperative adjuvant chemotherapy.
(A) According to p53 gene mutation status and (B) according to the p53 aberration group.
Fig 3.
TaqMeth value of PGP9.5, NMDAR2B, and CCNA1 in pStage II/III gastric cancer.
(A) Methylation of the indicated genes was analyzed using Q-MSP and TAqMeth values in tumors with p53 wild type were compared with those with p53 mutation. The threshold value for determination that a gene was methylated was determined as the maximum TaqMeth value of p53 wild type. (B) Tumors with p53 wild type or p53 mutation were compared in terms of the presence of super-high methylation of the indicated genes. Super-high methylation was defined that at least one gene showed higher TaqMeth value than each threshold values among three genes.
Fig 4.
Immunohistochemical expression of PGP9.5, NMDAR2B, and CCNA1 in gastric cancer according to their methylation status.
Immunohistochemical staining of PGP9.5, NMADR2B, and CCNA1 in primary tumor with or without hypermethylation of the promoter region of the corresponding gene (original magnification, X100, scale bars, 100 μm).
Table 2.
Clinicopathological characters of recurrent tumors of pStage II/III gastric cancer in the p53 aberrant group (A) and the p53 non-aberrant group (B).
Fig 5.
Kaplan-Meier analysis of 5 year RFS and Stage distribution in pStage II/III gastric cancer in the p53 aberrant and p53 non-aberrant groups.
(A) Survival curves for intestinal type were compared with those of diffuse type gastric cancer with pStage II/III. (B) Cancer stage distribution according to the p53 aberration group and histological findings.
Fig 6.
Epigenetic and/or chemotherapeutic treatments of the NUGC4 (wild type p53) and KATOIII (p53 null) gastric cancer cell lines.
NUGC4 and KATOIII cells were treated with the demethylating agent, 5-aza-2’-deoxycytidine (5-aza-dC) in the presence or absence of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), and in the presence or absence of the chemotherapeutic reagent, CDDP. 1A and 5A, 1 and 5 μM 5-aza-dC; T, TSA. Subsequently the cells were analyzed for: (A) p53 protein expression by Western Blotting. (B) A dual reporter assay to confirm p53 transcription activity. The dashed line indicates the optimal cut-off value (0.15) for determination of p53 activity. (C) Cell apoptosis was assayed using a Nexin Assay. A representative image is shown. Data are shown as the percentage of early and late apoptotic cells. *P<0.05, **<0.001, ***<0.0001.