Methylation-based mesothelioma diagnosis

During WCLC 2025, Janah Vandenhoeck presented the results of her research looking into the potential of a methylation-based assay to facilitate a better diagnosis of pleural mesothelioma.

Pleural mesothelioma is frequently diagnosed at advanced stages due to its insidious onset and nonspecific clinical presentation. The absence of reliable screening biomarkers and the limited sensitivity of imaging modalities in detecting early pleural or peritoneal involvement further contribute to diagnostic delays.

DNA methylation patterns differ significantly between tumor and healthy tissue, reflecting key epigenetic changes in cancer development. While healthy cells maintain tightly regulated methylation to control gene expression and preserve genomic stability, tumor cells often exhibit global hypomethylation alongside region-specific hypermethylation. These alterations create distinct methylation signatures that not only drive tumor progression but also serve as potential biomarkers for cancer diagnosis and prognosis. In her research, Ms Vandenhoeck wants to leverage these differences to create a new methylation-based diagnostic assay for pleural mesothelioma

By investigating the methylation patterns of mesothelioma, healthy lung tissue and other lung cancer subtypes, 1000s of differentially methylated CpG sites were identified. Using the Improved Methylation Profiling using Restriction Enzymes and smMIP Sequencing (IMPRESS) technology, this broad set of different was refined to a biomarker panel of 744 CpG sites. Subsequently, this panel was validated in 2 classifier models: one to discriminate tumoral from non-tumoral tissue (containing 310 CpG sites) and a second model allowing a discrimination between pleural mesothelioma and pleural metastasis (21 CpG sites). Both models performed very well with the first model having a sensitivity of 89% and a specificity of 94% and the second one having a sensitivity of 85% and a specificity of 100%.

As such, this methylation-based assay represents a promising diagnostic tool for pleural mesothelioma. Future research will focus on the use of liquid biopsy samples to allow a minimally invasive diagnosis of this devastating disease.