Frontiers in genetics · 2026
CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma.
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Zhang Ligong, Wang Bing, Zhang Mingliang
Аннотация
BACKGROUND: Lymph node metastasis (LNM) is a key prognostic determinant in thyroid carcinoma (THCA), yet molecular markers capturing intrinsic metastatic potential are limited.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.