Scientists have identified distinct protein profiles in encapsulated follicular-patterned thyroid tumors, which could revolutionize diagnosis and treatment. A study employing shotgun proteome analysis on 46 tissue specimens—including invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC), non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and normal thyroid tissues—revealed significant differences in protein expression.

The research found that IEFVPTC, a malignant tumor, exhibits a unique protein signature that clearly distinguishes it from lower-risk tumors like NIFTP and WDT-UMP. In contrast, no significant discriminatory proteins were identified between NIFTP and WDT-UMP, suggesting a close biological similarity between these two low-risk classifications.

Key findings include:

Distinct Separation: Principal component analysis showed a clear separation between IEFVPTC and normal thyroid tissue, as well as between IEFVPTC and the low-risk NIFTP/WDT-UMP group.

Differentially Expressed Proteins (DEPs): IEFVPTC had the highest number of DEPs compared to other tumor types, with 181 DEPs identified between IEFVPTC and non-IEFVPTC samples.

Top DEPs in IEFVPTC: Six proteins were upregulated (NPAPI, STK33, 05112, DLG4, THUM2, CODA1) and four were downregulated (CCHCR, STAR5, DDX6, LIGO2) in IEFVPTC compared to NIFTP/WDT-UMP.

Biological Pathways: DEPs in IEFVPTC were significantly associated with critical thyroid tumor progression pathways, including cell proliferation, cytoskeleton maintenance, cell-cell junction regulation, and signaling pathways such as TGF-beta, WNT, VEGF, mTOR, NF-$kappa$B, PI3K-Akt, MAPK, and RAS.

Hub Genes: The study identified hub genes like CUL1, PRKDC, DLG4, VAV2, FLNC, UBR5, MAST3, SRSF1, and SIN3B, some of which are linked to immune checkpoint inhibitor therapy response (PRKDC) and potential prognostic markers (CUL1, VAV2).

Tumorigenesis Trajectory: The proteomic profile suggests a linear progression from normal thyroid tissue to WDT-UMP and NIFTP, eventually leading to the malignancy of IEFVPTC, supporting the hypothesis that NIFTP/WDT-UMP may be precursors to IEFVPTC.

This pioneering proteomic analysis provides crucial insights into the tumor biology of follicular-patterned thyroid neoplasms, offering a foundation for developing new diagnostic tools and therapeutic strategies. Future research will involve validating these protein markers in larger patient cohorts and incorporating multi-omic data to further enhance understanding.

This publication received an award for graduate students who completed their studies on time and had international publications, 1st time, Academic Year 2567