Examination of pathway crosstalk and functional modules in papillary thyroid cancer dedifferentiation to anaplastic thyroid cancer

Sammanfattning: Thyroid cancer, comprising well-differentiated follicular and papillary types, alongside less common medullary and anaplastic subtypes with poor prognoses, exhibits specific anaplastic cases resulting from papillary dedifferentiation, lacking precise molecular evidence. Utilizing Metascape, CTpathway and PathwAX II, the study integrates functional modules and pathway crosstalk for dedifferentiation analysis, conducting a comprehensive two-dimensional assessment of toolset’s functionality, compatibility, and interoperability. Results suggest that transitions between the cancer subtypes involve pathways related to cellular processes, extracellular matrix interactions, and genetic alterations. Metascape enriched crosstalk tool findings, providing extended lists of specific pathways, while CTpathway exhibited better sensitivity and specificity, offering more result customization options and database selection than PathwAX II. PathwAX II, with unique interactive features for network display and identifying depleted pathways, emerges a valuable component in a comprehensive pipeline integrating these three tools. Additional validation against previous clinical studies affirms the reliability of the results, reinforcing PathwAX II’s role as a key reference point in the creation of such a pipeline. The study also suggests future tool development directions, highlighting strengths and limitations across the platforms. The detailed pathway and gene analysis contributes concrete knowledge to the scientific community, serving as a hallmark for future studies.