# Subtype-Dependent Expression Patterns of Core Hippo Pathway Components in Thymic Epithelial Tumors (TETs): An RT-qPCR Study

## TL;DR

This study finds that different types of thymic tumors show distinct patterns in the expression of key Hippo pathway genes, suggesting potential biomarkers for classification.

## Contribution

The study identifies subtype-specific expression patterns of Hippo pathway components in thymic epithelial tumors using RT-qPCR.

## Key findings

- YAP1 and TEAD4 are upregulated in specific TET subtypes, particularly in type A and B3 thymomas and thymic carcinoma.
- Upstream Hippo kinases like MST1 and LATS1 are reduced in thymic carcinoma compared to other subtypes.
- SAV1 is elevated in type A and B3 TETs, while MOB1A remains near baseline across subtypes.

## Abstract

Background/Objectives: Thymic epithelial tumors (TETs) are rare, histologically heterogeneous neoplasms lacking robust molecular biomarkers. Hippo pathway dysregulation—driving YAP/TEAD-dependent transcription—has been implicated across cancers, but transcript-level data in TETs are limited. Methods: We profiled 26 (23 TETs and three normal thymus) formalin-fixed and paraffin-embedded (FFPE) specimens by SYBR real-time quantitative polymerase chain reaction (RT-qPCR) across World Health Organization (WHO) subtypes, focusing on core Hippo components YAP1, TEAD4, MST1, SAV1, LATS1, and MOB1A. Expression was normalized to the geometric mean of HPRT1 and TBP and reported as log2 fold change (log2FC) using the 2−ΔΔCq method relative to the pooled normal. Group differences were compared using non-parametric tests. Results: Median log2FC values showed subtype-dependent upregulation of YAP1/TEAD4, notably in type A (YAP1 ≈ +3.43) and B3 (YAP1 ≈ +2.78) thymomas, with TEAD4 strongly increased in thymic carcinoma (TC; ≈ +3.49) and elevated in type A/B3. Upstream kinases tended to be subtype-specifically reduced, particularly in TC (MST1 ≈ −1.38; LATS1 ≈ −1.34), and modestly in B1. SAV1 was elevated in type A (≈+2.25) and B3 (≈+2.01), while MOB1A remained near baseline. Differential expression among WHO subtypes (Kruskal–Wallis) was significant for YAP1 (p = 0.003), TEAD4 (p = 0.015), SAV1 (p = 0.004), MST1 (p = 0.012), and LATS1 (p = 0.036), but not for MOB1A (p = 0.09). Conclusions: TETs seem to exhibit subtype-dependent expression patterns of core Hippo pathway components, characterized by enhanced YAP1–TEAD4 transcriptional output in selected subtypes and marked reduction of the MST1/LATS1 kinase module, most pronounced in TC. These exploratory patterns nominate candidate markers for subtype stratification and clinical validation.