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Published on: February 8, 2018
The thyroid hormone activating enzyme, DIO2, is a potential pan-cancer biomarker and immunotherapy target
A Nappi1, C Miro2, A G Cicatiello2
1Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131, Naples, Italy. annarita.nappi@unina.it.
Purpose:
Type 2 deiodinase (D2), encoded by DIO2 gene, catalyzes the activation of the prohormone thyroxine (T4) into the bioactive hormone triiodothyronine (T3) in peripheral tissues, thereby regulating the intracellular Thyroid Hormone (TH) availability. Recently, several studies have demonstrated that a drastic increase in the peripheral activation of TH, via D2, fosters tumor progression, metastasis, and immunity.
Methods:
To further prove the clinical relevance of D2 in human cancer, based on public Database of The Cancer Genome Atlas (TCGA), we conducted a pan-cancer analysis of DIO2 expression in various cancer types and investigated the association of DIO2 expression with the tumor microenvironment (TME) components and immune cell infiltration, along with the DIO2 genetic alteration types.
Results:
Although with different expression levels between the various cancer types, the pan-cancer analysis showed that DIO2 was highly expressed in most tumors and related to the progression of some tumor types. Furthermore, DIO2 expression was also significantly correlated with TME components, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets.
Conclusion:
The relevance of this study is that it adds a clinical relevance to the recent demonstrations that D2 accelerates tumor invasion in animal models and poses DIO2 gene as a potential prognostic marker in various human cancers.
Insights
The DIO2 gene, crucial for thyroid hormone activation, is highly expressed in many cancers and linked to tumor progression. This suggests DIO2 may serve as a prognostic marker in human cancers.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- Type 2 deiodinase (D2) activates thyroxine (T4) to triiodothyronine (T3), regulating intracellular thyroid hormone (TH) availability.
- Increased peripheral TH activation via D2 has been linked to tumor progression, metastasis, and immune modulation.
- The DIO2 gene encodes the D2 enzyme, playing a key role in TH metabolism.
Purpose of the Study:
- To investigate the clinical relevance of D2 in human cancers.
- To conduct a pan-cancer analysis of DIO2 gene expression using The Cancer Genome Atlas (TCGA) database.
- To explore the association between DIO2 expression, tumor microenvironment (TME) components, and immune cell infiltration.
Main Methods:
- Pan-cancer analysis of DIO2 expression across various cancer types from TCGA data.
- Investigation of correlations between DIO2 expression and TME characteristics.
- Analysis of the relationship between DIO2 expression and immune cell infiltration patterns.
- Examination of DIO2 genetic alteration types and their impact.
Main Results:
- DIO2 was found to be highly expressed in the majority of analyzed tumors, though expression levels varied.
- DIO2 expression correlated with the progression of certain tumor types.
- Significant associations were observed between DIO2 expression and TME components, immune cell infiltration, and immune gene subsets (both inhibitory and stimulatory).
Conclusions:
- The study provides clinical relevance to findings that D2 activity promotes tumor invasion.
- The DIO2 gene emerges as a potential prognostic biomarker for various human cancers.
- Understanding DIO2's role can inform cancer diagnostics and therapeutic strategies.
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