Department of Immunology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Life Sci. 2020 Aug 1;254:117774. doi: 10.1016/j.lfs.2020.117774. Epub 2020 May 11.
Gastric cancer (GC) remains one of the deadliest malignancies worldwide due to its poor prognosis. DNA methylation changes, as an early event during tumor progression, constitute attractive markers for cancer diagnostics. In the current study, CD40 DNA methylation was investigated in GC as a novel epigenetic biomarker.
We first analyzed DNA methylation microarrays from the Gene Expression Omnibus database on GC samples to evaluate the potential diagnostic value of CD40 methylation. Moreover, using q-MSP, in a set of internal samples including GC primary tumors and adjacent normal specimens, CD40 DNA methylation levels were determined. The Cancer Genome Atlas (TCGA) data on GC was also analyzed for further validation.
Our results illustrated significant CD40 hypermethylation in GC samples compared to normal specimens which was significantly correlated with the clinical stage of malignancy. Besides, the high accuracy of CD40 methylation as a diagnostic biomarker in GC was confirmed using the ROC curve analysis with an AUC value of 0.9089. Also, gene set enrichment analysis showed that CD40 is mainly involved in biological processes regulating immune response activation in GC. Further analysis of other prevalent cancer entities in TCGA showed that CD40 hypermethylation is a common event during tumor progression and could be considered as a potential biomarker for the detection of breast, colorectal, and prostate cancers as well.
The finding of this study suggests that CD40 methylation as a potential pan biomarker could be a valuable target for liquid biopsy application of human cancers.
由于预后较差，胃癌（GC）仍然是全球最致命的恶性肿瘤之一。DNA 甲基化改变作为肿瘤进展过程中的早期事件，构成了癌症诊断有吸引力的标志物。在本研究中，我们研究了 GC 中的 CD40 甲基化作为一种新的表观遗传生物标志物。
我们首先分析了来自基因表达综合数据库（GEO）的 GC 样本的 DNA 甲基化微阵列，以评估 CD40 甲基化的潜在诊断价值。此外，我们还使用 q-MSP 在包括 GC 原发性肿瘤和相邻正常标本的一组内部样本中确定 CD40 DNA 甲基化水平。还对癌症基因组图谱（TCGA）数据库中的 GC 数据进行了进一步验证。
与正常标本相比，GC 样本中的 CD40 呈显著高甲基化，且与恶性肿瘤的临床分期显著相关。此外，ROC 曲线分析证实 CD40 甲基化作为 GC 诊断生物标志物具有很高的准确性，AUC 值为 0.9089。此外，基因集富集分析表明，CD40 主要参与 GC 中调节免疫反应激活的生物学过程。对 TCGA 中其他常见癌症实体的进一步分析表明，CD40 高甲基化是肿瘤进展过程中的常见事件，可被视为检测乳腺癌、结直肠癌和前列腺癌的潜在生物标志物。
本研究的结果表明，CD40 甲基化作为一种潜在的泛癌生物标志物，可能是人类癌症液体活检应用的有价值的靶标。
