CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma

Lymph node metastasis (LNM) is a key prognostic determinant in thyroid carcinoma (THCA), yet molecular markers capturing intrinsic metastatic potential are limited.

Generalized additive models were applied to TCGA-THCA data to screen for genes with diametrically opposite expression-tumor diameter relationships between N0 and N1 patients. CENPM was subsequently validated in independent transcriptomic cohorts, spatial transcriptomics, and immunohistochemistry. Single-cell transcriptomics, in silico knockout, drug repositioning, and molecular docking were employed to dissect its immunological roles and therapeutic relevance.

CENPM expression increased with tumor diameter in N0 but decreased in N1, and high CENPM was associated with poorer disease-free survival. CENPM was predominantly enriched in CD8⁺ naïve and effector T cells, particularly in anaplastic carcinoma. Virtual knockout predicted downstream transcriptional changes associated with lymphocyte activation, translational machinery, and immune effector pathways. Drug repositioning identified filgotinib as a candidate to reverse the CENPM-high signature, with stable CENPM-filgotinib binding confirmed by docking and molecular dynamics.

CENPM shows diametrically opposite expression-diameter relationships between N0 and N1 patients, suggesting a shift in biological behavior upon nodal involvement, with potential therapeutic relevance.