BACKGROUND 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). MATERIAL AND METHODS 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. RESULTS GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 x 10-4), 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. CONCLUSIONS 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.

中文翻译：

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重症肌无力患者胸腺中GHSR甲基化水平的调查。

背景技术在人类癌症中越来越多地观察到生长激素促分泌素受体基因（GHSR）的超甲基化，这表明它可能代表了具有临床意义的泛癌生物标志物。然而，关于胸腺上皮肿瘤，尤其是重症肌无力（TAMG）患者的胸腺瘤中GHSR甲基化水平的了解仍很少。材料与方法在本研究中，我们收集了65名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名患者的邻近健康胸腺组织的DNA样本。然后，我们调查了收集到的组织中的GHSR甲基化水平，以寻找与样品临床特征的相关性。结果与健康的胸腺组织（P <1 x 10-4）相比，在18个胸腺瘤样品（28％）中观察到了GHSR甲基化，并且这些样品在疾病晚期比I期（94％在II期或II期）更为丰富。更高）。其余的47个胸腺瘤，所有研究的健康胸腺样品和循环淋巴细胞中的GHSR均被去甲基。结论GHSR高甲基化不是TAMG中的泛癌标志物或早期事件，而是发生在其中近1/4中，且主要发生在II期以后。需要进行后续研究来阐明导致TAMG组织中GHSR甲基化过度的分子途径及其与疾病进展的相关性。其余的47个胸腺瘤，所有研究的健康胸腺样品和循环淋巴细胞中的GHSR均被去甲基。结论GHSR高甲基化不是TAMG中的泛癌标志物或早期事件，而是发生在其中近1/4中，且主要发生在II期以后。需要进行后续研究来阐明导致TAMG组织中GHSR甲基化过度的分子途径及其与疾病进展的相关性。其余的47个胸腺瘤，所有研究的健康胸腺样品和循环淋巴细胞中的GHSR均被去甲基。结论GHSR甲基化不是TAMG中的泛癌标志物或早期事件，而是发生在其中近1/4中，主要发生在II期以后。需要进行后续研究来阐明导致TAMG组织中GHSR甲基化过度的分子途径及其与疾病进展的相关性。