The Journal of Clinical Endocrinology and Metabolism Journal Article

CD133 Expression and MTC Prognosis

November 02, 2020
 

Alfonso Cordero-Barreal, Eduardo Caleiras, Evangelina López de Maturana, María Monteagudo, Ángel M Martínez-Montes, Rocío Letón, Eduardo Gil, Cristina Álvarez-Escolá, Rita M Regojo, Víctor Andía, Mónica Marazuela, Sonsoles Guadalix, María Calatayud, Luis Robles-Díaz, Miguel Aguirre, Juana M Cano, José Ángel Díaz, Pilar Saavedra, Cristina Lamas, Sharona Azriel, Julia Sastre, Javier Aller, Luis J Leandro-García, Bruna Calsina, Juan María Roldán-Romero, María Santos, Javier Lanillos, Alberto Cascón, Cristina Rodríguez-Antona, Mercedes Robledo, Cristina Montero-Conde
The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 11, November 2020, dgaa527
https://doi.org/10.1210/clinem/dgaa527

Abstract

Context

The identification of markers able to determine medullary thyroid cancer (MTC) patients at high-risk of disease progression is critical to improve their clinical management and outcome. Previous studies have suggested that expression of the stem cell marker CD133 is associated with MTC aggressiveness.

Objective

To evaluate CD133 impact on disease progression in MTC and explore the regulatory mechanisms leading to the upregulation of this protein in aggressive tumors.

Patients

We compiled a series of 74 MTCs with associated clinical data and characterized them for mutations in RET and RAS proto-oncogenes, presumed to be related with disease clinical behavior.

Results

We found that CD133 immunohistochemical expression was associated with adverse clinicopathological features and predicted a reduction in time to disease progression even when only RET-mutated cases were considered in the analysis (log-rank test P < 0.003). Univariate analysis for progression-free survival revealed CD133 expression and presence of tumor emboli in peritumoral blood vessels as the most significant prognostic covariates among others such as age, gender, and prognostic stage. Multivariate analysis identified both variables as independent factors of poor prognosis (hazard ratio = 16.6 and 2; P = 0.001 and 0.010, respectively). Finally, we defined hsa-miR-30a-5p, a miRNA downregulated in aggressive MTCs, as a CD133 expression regulator. Ectopic expression of hsa-miR-30a-5p in MZ-CRC-1 (RETM918T) cells significantly reduced CD133 mRNA expression.

Conclusions

Our results suggest that CD133 expression may be a useful tool to identify MTC patients with poor prognosis, who may benefit from a more extensive primary surgical management and follow-up.

Read the article

 

You may also like...

Publishing Benefits

Author Resource Center

We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Publishing Benefits

Author Resource Center

We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.

Thematic Issue

Latest Thematic Issue

immuno-endocrinology
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.

Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.

Back to top
Short on time?

We'll come to you...

Get updates on the latest breakthroughs, clinical practice guidelines, and career development opportunities, straight to your inbox

Then take the next step: Set up your free website account and get exclusive access to even more great tools & content!