Molecular mechanisms of thymopoietin in papillary thyroid cancer: Multiplatform gene expression data, gene knockout screening, and in-house immunohistochemistry

Although thymopoietin (TMPO) has been elucidated to be overexpressed in cancers, its underlying mechanisms are not yet fully understood.

To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma (PTC).

Databases such as Gene Expression Omnibus, The Cancer Genome Atlas Program-Genotype-Tissue Expression, The Human Protein Atlas (THPA), and tissue microarrays were screened. Immunohistochemical staining scores and standardized mean difference were used to calculate expression levels, and summary receiver operating characteristic curves were plotted to evaluate diagnostic performance. A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways. A protein interaction network was constructed to identify hub genes. The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats (CRISPR) knockout screening and the Cancer Cell Line Encyclopedia database.

The TMPO protein was significantly overexpressed in PTC tissues, primarily localized in the cytoplasm and nuclear membrane. The mRNA level analysis showed mild overexpression of TMPO in PTC tissues, with a certain discriminatory value (area under the curve = 0.66). TMPO may promote cancer through involvement in cell adhesion, focal adhesion, leukocyte migration, and multiple cancer-related signaling pathways. Additionally, CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines, indicating its important role in tumor growth.

TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.