Methylation and Expression of Retinoblastoma and Transforming Growth Factor-β1 Genes in Epstein-Barr Virus-Associated and -Negative Gastric Carcinomas

Abstract

Background. Retinoblastoma (RB) and transforming growth factor-β1 (TGF-β1) are important tumor-related factors. Methods. A series of 30 EBV-associated gastric carcinoma (EBVaGC) and 38 matched EBV-negative gastric carcinoma (EBVnGC) tissues were examined for the promoter methylation of RB by methylation-specific PCR (MSP) method. The expression of RB and TGF-β1 in gastric carcinoma tissues was detected by immunohistochemistry. Results. The methylation rate of RB gene in EBVaGC and EBVnGC was 80.0% (24/30) and 50.0% (19/38), respectively. The difference of RB methylation rate between EBVaGC and EBVnGC was significant (χ 2 = 6.490, P = 0.011). There was no significant difference for RB expression between EBVaGC (43.3%, 13/30) and EBVnGC (63.2%, 24/38), and also for TGF-β1 between EBVaGC (56.7%, 17/30) and EBVnGC (63.2%, 24/38). RB methylation was not reversely correlated with RB expression in gastric carcinoma tissues (χ 2 = 2.943, P = 0.086, r = 0.208). RB methylation, loss expression of RB, and TGF-β1 expression were significantly associated with tumor invasion and lymph node metastasis (P < 0.05), but was not associated with sex, age, histological subtype (differentiation status) and tumor location. Conclusions. Methylation of RB is a common event in gastric carcinomas and EBV induces methylation of RB in EBVaGC, which may contribute to the development of gastric carcinomas. EBV has no significant effect on induction of TGF-β1 expression. Detection of RB methylation, RB expression, and TGF-β1 expression may be helpful to judge the status of tumor invasion and lymph node metastasis in gastric carcinomas.

The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas

“…Bisulfite modification of DNA was carried out as described previously [ 24 ]. The methylation status of BARF1 and BHRF1 promoters was determined using methylation-specific PCR (MSP) [ 22 , 24 ].…”

Alteration in Methylation Pattern of Retinoblastoma 1 Gene Promotor Region in Intestinal Metaplasia with or without Helicobacter pylori and Gastric Cancer Patients

“…However methylation studies on the promoter region of RB1 gene in relation to the GC and its pathogenesis are limited. In some of the studies, Zhao et al [20] found that the percent of positive methylation bands for RB1 gene was 44.6%, similar to Liu et al [21] study of EBV-negative gastric carcinoma (EBVnGC) (50%), but less than that of EBV-associated gastric carcinoma (EBVaGC) cases (80%), which provides further support that EBV induces RB1 gene methylation in EBVaGC. However, there are no studies about RB1 gene methylation in GC and IM with or without H. pylori infection.…”

Methylation of Epstein-Barr Virus-Associated Gastric Cancer Suppressor Genes

“…silent genes involved by EBV may be related to the occurrence of EBV-related gastric cancers [21]. This study found that LOXL1 gene promoter was hypermethylated in EBV-related gastric cancer tissues, indicating that DNA methylation status in LOXL1 gene regulation region is an essential regulatory mechanism of gene expression [22]. The MSP results show that LOXL-1 promoter was fully methylated in EBV positive gastric cancer cell lines GT38 and PT, partially methylated in EBV positive cell lines (B95-8, Raji, GT39 and SNU719), and unmethylated in EBV negative gastric cancer cell lines SGC7901 and HGC27.…”