Department of Translational Research and of New Surgical and Medical Technologies, Lab. of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy.
Department of Translational Research and of New Surgical and Medical Technologies, Lab. of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy.
Gene. 2020 Aug 20;752:144774. doi: 10.1016/j.gene.2020.144774. Epub 2020 May 19.
Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG).
In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples.
GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes.
GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression.
生长激素促分泌素受体基因（GHSR）的高甲基化在人类癌症中越来越常见，这表明它可能是一种具有临床意义的泛癌生物标志物。然而，关于胸腺瘤中 GHSR 甲基化水平，尤其是在重症肌无力合并胸腺瘤（TAMG）患者的胸腺瘤中，人们知之甚少。
在本研究中，我们收集了 65 例 TAMG 患者的循环淋巴细胞和手术切除的肿瘤组织以及其中 43 例患者的相邻健康胸腺组织的 DNA 样本。然后，我们在收集的组织中研究 GHSR 甲基化水平，寻找与样本临床特征的相关性。
与健康胸腺组织相比（P<1×10），18 例胸腺瘤样本（28%）中观察到 GHSR 高甲基化，这些样本在晚期疾病阶段比 I 期（94%在 II 期或更高）更为丰富。47 例其余胸腺瘤、所有研究的健康胸腺样本和循环淋巴细胞中 GHSR 去甲基化。
GHSR 高甲基化不是 TAMG 的泛癌标志物或早期事件，但在近 1/4 的 TAMG 中发生，主要发生在 II 期以后。需要进一步研究来阐明导致 TAMG 组织中 GHSR 高甲基化的分子途径及其与疾病进展的相关性。
