Honing in on thyroid cancer

A closer look at gene expression in papillary thyroid cancer opens new opportunities for its detection.

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In their quest to understand the root causes of thyroid cancer, researchers around the world have increasingly turned their attention to PAX8: a member of a family of proteins involved in transcribing information from DNA, that are closely linked to embryonic development and cancer growth. PAX8 plays a critical role in the development and function of the thyroid gland and its expression is often reduced in patients with thyroid carcinoma. 

Francesca Rosignolo and co-workers in Italy compared the expression of 11 genes thought to be controlled by PAX8 in papillary thyroid carcinoma (PTC) ‑ the most common type of thyroid cancer worldwide, accounting for 70 to 80% of all cases.  

Rosignolo and her team’s study yields new insights into genes of particular interest as potential thyroid cancer biomarkers. “We identified several PAX8 target genes that were significantly over, or underexpressed, in PTC tissues as compared with normal thyroid tissues, and some were specifically associated with tumour aggressiveness,” she explains.  

Five of the 11 genes displayed notable differences in transcript levels, a reliable measure of gene activity, in tumour tissues compared to normal thyroid tissues, reinforcing the idea that they have a key involvement in the development of PTC. The research team also singled out two genes that hold potential to improve detection and prognosis of thyroid cancer: the lipocalin 2 (LCN2) gene, which was found to be markedly overexpressed, and the glypican 3 (GPC3) gene, which was notably underexpressed in tumour tissue compared with normal tissue.  

Based on advanced protein analysis, the researchers found that the protein coded for by the GPC3 gene could be detected in all normal tissue but in none of the tumour tissue samples. This finding implies that staining for the GPC3 protein could offer an effective way to distinguish between normal and papillary thyroid cancer cells.  

Although developing and validating biomarkers is “a long, arduous task,” Rosignolo is confident that “these preliminary results from our study suggest that the expression of certain PAX8 target genes might in future be assessed to diagnose PTCs and/or identify tumours that may need particularly close surveillance.” 

“Our next research projects will focus mainly on the identification and validation of biomarkers that can accurately predict PTC aggressiveness and recurrence in the early stages,” says Rosignolo.

 She emphasises that international collaboration is “fundamental for stimulating scientific progress and improving our knowledge of cancer. Advances in communication technologies have certainly facilitated this approach, but more efforts are needed to break down barriers.”

References

  1. Rosignolo, F., Sponziello, M., Durante, C., Puppin, C., Mio, C. et al. Expression of PAX8 target genes in papillary thyroid carcinoma. PLoS ONE. (2016). | article

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