Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a low-risk thyroid tumor with a favorable prognosis.

Nonetheless, differentiating NIFTP from other thyroid tumors remains challenging, necessitating reliable diagnostic markers.

This study is aimed at discovering NIFTP-specific mRNA markers through RNA sequencing analysis of thyroid tumor tissues.

We performed mRNA expression profiling for 74 fresh frozen thyroid tissue samples, including NIFTP and benign and malignant follicular-cell-derived tumors.

NIFTP/malignant tumors showed 255 downregulated genes and 737 upregulated genes compared to benign tumors.

Venn diagram analysis revealed 19 significantly upregulated and 7 downregulated mRNAs in NIFTP.

Akaike information criterion analysis allowed us to select OCLN , ZNF423 , LYG1 , and AQP5 mRNA markers.

We subsequently developed a predictive model based on logistic regression analysis using these four mRNAs, which we validated in independent samples ( n  = 90) using a qRT-PCR assay.

This model demonstrated high accuracy in predicting NIFTP in discovery dataset (AUC (area under the receiver operating characteristic) = 0.960) and the validation dataset (AUC = 0.757).

Our results suggest that OCLN , ZNF423 , LYG1 , and AQP5 mRNA markers might serve as reliable molecular markers for identifying NIFTP among other thyroid tumors, ultimately aiding in accurate diagnosis and management of NIFTP patients.