Abstract
Simple SummaryThis study aimed to evaluate the clinicopathologic significance of CD73 expression in patients with papillary thyroid carcinoma (PTC) and the potential for CD73 to serve as a therapeutic target of PTC. CD73 was highly expressed in PTC, but not in the normal thyroid tissue. Overexpression of CD73 was associated with unfavorable clinicopathologic characteristics and a shorter recurrence-free survival. The expression level of CD73 mRNA was associated with the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes. CD73 inhibitor attenuated PTC cell proliferation, migration, and invasion in vitro, and suppressed PTC xenograft tumor growth in nude mice. These results suggest that CD73 expression is an unfavorable prognostic marker for patients with PTC. CD73 blockade would be an attractive candidate for therapeutic strategies in patients with advanced PTC.CD73 is involved in tumor immune escape and promotes the growth and progression of cancer cells. The functional role of CD73 expression in papillary thyroid carcinoma (PTC) has not yet been established. In 511 patients with PTC, immunohistochemistry for CD73 on tissue microarrays showed that the high expression of CD73 was associated with an aggressive histologic variant (p = 0.002), extrathyroidal extension (p < 0.001), lymph node metastasis (p < 0.001), and BRAFV600E mutation (p = 0.015). Survival analysis results showed that patients with high CD73 expression had worse recurrence-free survival (p = 0.023). CD73 inhibitors induced G1 cell cycle arrest and apoptosis, inhibited the migration and invasion of PTC cells, and suppressed tumor growth in PTC xenograft nude mice. High expression of CD73 (NT5E) mRNA was associated with unfavorable clinicopathologic characteristics, the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes in The Cancer Genome Atlas (TCGA) dataset. Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73–adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.
Highlights
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, accounting for more than90% of all cases [1,2]
Membranous staining in cancer cells was considered positive
High expression of CD73 protein by cancer cells was associated with poor clinicopathologic features including extrathyroidal extension, lymph node metastasis, BRAFV600E
Summary
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, accounting for more than90% of all cases [1,2]. Most patients with PTC have an excellent prognosis with a 10-year survival rate of more than 90–95% [2,3]. PTC recurrence is, a major adverse event after initial treatment, and ranges widely from 1% to 40% depending on the clinicopathological features and molecular signature, when harboring mutation BRAFV600E in combination with TERT promoter [1]. Cancer cells communicate with surrounding stromal cells including fibroblasts, lymphatic and vascular endothelial cells, pericytes, adipocytes, and immune cells [5]. The tumor microenvironment consisting of cancer cells and stromal cells induces immune tolerance and tumor angiogenesis, and regulates biological processes such as tumor growth, progression, and evolution [5,6,7,8,9]
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