Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma

Open Med (Wars). 2025 Oct 23;20(1):20251283. doi: 10.1515/med-2025-1283. eCollection 2025.

Abstract

Background: Papillary thyroid carcinoma (PTC) generally exhibits favorable prognosis; however, a subset of patients remains at risk for recurrence. Serine protease 2 (PRSS2) was an oncogenic factor in several solid tumors, yet its expression profile and functional role in PTC remain poorly defined. This study aimed to investigate the expression level of PRSS2 in PTC and its prognostic significance, as well as explore its potential involvement in immune regulatory mechanisms.

Methods: PTC specimens from thyroidectomy patients were analyzed by transcriptomic analysis, quantitative real-time PCR, and immunohistochemistry. Differential gene expression and survival analyses were performed by integrating data from TCGA and GEO databases. Pearson correlation analysis was utilized to evaluate associations between PRSS2 and immune-related genes.

Results: PRSS2 was upregulated in PTC tissues. High PRSS2 expression was associated with better survival (HR = 3.253; 95% CI: 1.155-9.160), especially in patients aged ≥62 and stage II/III. Patients with low PRSS2 and high BRAF expression exhibited a markedly reduced 5-year overall survival rate. PRSS2 also showed significant positive correlations with multiple immune-related genes, including a moderate to strong correlation with T-cell receptor beta variable (TRBV) region genes (R = 0.58-0.72), CD40, and transforming growth factor beta-stimulated clone 22 domain 1.

Conclusions: PRSS2 is upregulated in PTC and is associated with favorable prognosis. Its association with TRBV and other immune-related genes suggests a correlation with tumor immune microenvironment. Further studies are needed to elucidate the biological functions of PRSS2 in PTC and to assess therapeutic potential.

Keywords: CD40; PRSS2; TRBV; TSC22D1; papillary thyroid carcinoma; prognostic value.