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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genomics

Background:

• Thymic epithelial tumors (TETs) are rare and lack specific molecular biomarkers.
• Hippo pathway dysregulation, particularly YAP/TEAD transcriptional activity, is implicated in various cancers.
• Limited transcript-level data exists for the Hippo pathway in TETs.

Purpose of the Study:

• To investigate the expression patterns of core Hippo pathway components in different World Health Organization (WHO) subtypes of TETs.
• To identify potential molecular biomarkers for TET subtype stratification.

Main Methods:

• SYBR real-time quantitative polymerase chain reaction (RT-qPCR) was performed on 23 TET and 3 normal thymus FFPE specimens.
• Expression levels of YAP1, TEAD4, MST1, SAV1, LATS1, and MOB1A were quantified.
• Data was normalized and analyzed using the 2^-ΔΔCq method and non-parametric tests for differential expression across WHO subtypes.

Main Results:

• Subtype-dependent upregulation of YAP1 and TEAD4 was observed, notably in thymoma types A and B3, and thymic carcinoma (TC).
• The upstream kinases MST1 and LATS1 were significantly reduced, particularly in TC.
• SAV1 expression was elevated in types A and B3, while MOB1A remained near baseline; differential expression was significant for YAP1, TEAD4, SAV1, MST1, and LATS1 across subtypes.

Conclusions:

• TETs exhibit distinct expression profiles of Hippo pathway components correlating with histological subtypes.
• Enhanced YAP1-TEAD4 transcriptional output and reduced MST1/LATS1 kinase activity characterize specific TET subtypes, especially TC.
• These findings nominate candidate molecular markers for TET subtype stratification and warrant further clinical validation.