Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types

Ye-Peng Wang ¹, Chao Ma ², Xue-Kun Yang ³

⁰Department of Neurosurgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Frontiers in Genetics +

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February 9, 2024

View abstract on PubMed

Summary

Thyroid hormone receptor-associated protein 3 (THRAP3) shows varied expression across cancers. While a prognostic biomarker in some, THRAP3 may be protective in lung adenocarcinoma and lung squamous cell carcinoma.

Area Of Science

Molecular biology
Oncology
Bioinformatics

Background

Thyroid hormone receptor-associated protein 3 (THRAP3) plays roles in DNA damage response, pre-mRNA processing, and nuclear export.
The pan-cancer biological activities of THRAP3 are largely unexplored.
This study investigates THRAP3 expression and its clinical significance in various cancers, with a focus on lung cancer.

Purpose Of The Study

To conduct a comprehensive pan-cancer analysis of THRAP3 expression and its correlation with clinical outcomes and the tumor microenvironment.
To validate THRAP3 protein levels in lung cancer tissues.
To investigate THRAP3 expression within specific cell types in lung adenocarcinoma using single-cell sequencing.

Main Methods

Pan-cancer analysis utilizing bioinformatics databases to correlate THRAP3 expression with clinical data and tumor microenvironment.
Immunohistochemistry (IHC) to assess THRAP3 protein levels in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
Single-cell RNA sequencing (ScRNA-seq) to analyze cell type proportions and THRAP3 expression in LUAD tissues.

Main Results

THRAP3 is upregulated in several cancer types but underexpressed in LUSC.
IHC confirmed low THRAP3 expression in LUAD and LUSC.
THRAP3 expression correlated with prognosis differently across cancers: poor in kidney renal clear cell carcinoma, prolonged survival in kidney chromophobe, brain lower-grade glioma, and skin cutaneous melanoma.
Single-cell analysis revealed increased T/B cells, macrophages, and fibroblasts in LUAD, with THRAP3 specifically overexpressed in mast cells.

Conclusions

THRAP3 emerges as a potential prognostic biomarker and immunotherapeutic target in multiple cancers.
However, THRAP3 may function as a protective gene in LUAD and LUSC, indicated by its low expression.
Further research is warranted to elucidate the dual role of THRAP3 in cancer development and progression.

Keywords:

biomarker immune infiltration pan-cancer prognosis single cell