CD40 DNA hypermethylation in primary gastric tumors; as a novel diagnostic biomarker.

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.

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Declaration of competing interest The authors declare that there are no conflicts of interest.