Abstract
Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light of novel blood-based assays. DNA methylation in cancer has been linked to tumorigenesis, but its value as a biomarker has not been fully explored. In this study, we have investigated the methylation patterns of the Gasdermin E gene across 14 different tumor types using The Cancer Genome Atlas (TCGA) methylation data (N = 6502). We were able to identify six CpG sites that could effectively distinguish tumors from normal samples in a pan-cancer setting (AUC = 0.86). This combination of pan-cancer biomarkers was validated in six independent datasets (AUC = 0.84–0.97). Moreover, we tested 74,613 different combinations of six CpG probes, where we identified tumor-specific signatures that could differentiate one tumor type versus all the others (AUC = 0.79–0.98). In all, methylation patterns exhibited great variation between cancer and normal tissues, but were also tumor specific. Our analyses highlight that a Gasdermin E methylation biomarker assay, not only has the potential for being a methylation-specific pan-cancer detection marker, but it also possesses the capacity to discriminate between different types of tumors.
Highlights
Cancer is the second leading cause of death worldwide with 9.6 million deaths and 17 million new cases occurring yearly [1]
We explored the capacity of Gasdermin E (GSDME) methylation to differentiate between different tumor types preliminary testing showed the highest average area under the curve (AUC), with the least number of predictors, and the based on the combinations of CpG probes
We previously reported that GSDME methylation is a potential biomarker for the diagnosis of breast [39,40] and colorectal cancers [38]
Summary
Cancer is the second leading cause of death worldwide with 9.6 million deaths and 17 million new cases occurring yearly [1]. The five most prevalent cancers worldwide, include lung, breast, colorectal, prostate, and gastric cancer [1]. Despite advances in diagnosis and treatment, the socio-economic burden of cancer still weighs heavily on societies worldwide. Accurate, and cost-effective diagnostic strategies are needed for improved treatment and optimal disease management [2,3,4]. The use of biologically identifiable characteristics, more commonly known as biomarkers, to indicate the presence of cancer in the body has gained considerable attention. Studies have examined several sources of biomarkers, including DNA mutations, metabolites, gene and protein expression, mRNA, imaging, and antibodies amongst others [5,6,7]
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