Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil.
Disciplina de Gastroenterologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Epigenetics. 2022 Jan;17(1):110-116. doi: 10.1080/15592294.2021.1878724. Epub 2021 Feb 8.
Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, , in clinical samples. expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced mRNA levels and increased exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy. AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; : beta-2-microglobulin; : glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; : leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1.
胃癌（GC）是全球致死率最高的癌症类型之一。对癌细胞进行表观遗传操作是更好地理解基因表达调控机制的有用工具，并有助于发现新的生物标志物。我们的研究小组最近报道了一组 83 个可能在 GC 细胞系中受 DNA 甲基化调控的基因。在此，我们进一步研究了其中一个基因 在临床样本中的调控。通过 RT-qPCR 评估 表达，通过下一代亚硫酸氢盐测序研究 36 个 GC 及配对的相邻非肿瘤组织样本中的 DNA 甲基化。我们表明， mRNA 水平降低和外显子甲基化增加均与未分化和低分化肿瘤相关。此外，+45 外显子 CpG 位点的 基因表达和甲基化水平呈负相关。我们认为 DNA 过度甲基化可能导致未分化和低分化 GC 中 表达降低。因此，我们的结果表明，一些基因可能有助于分层那些更有可能从表观遗传治疗中受益的患者。AR：雄激素受体；5-AZAdC：5-aza-2'-脱氧胞苷；：β-2-微球蛋白；：甘油醛-3-磷酸脱氢酶；GC：胃癌；GLM：一般线性模型；：富含亮氨酸重复序列 37 成员 A2；SD：标准偏差；TFII-I：一般转录因子 II-I；TSS：转录起始位点；XBP1：X 框结合蛋白 1。
