Novel Biomarker Could Improve Papillary Thyroid Cancer Monitoring

A large noncoding RNA (LincRNA) in the thyroid peroxidase (TPO) gene may be a novel biomarker that could potentially be used to monitor patients with papillary thyroid cancer (PTC) undergoing targeted therapies, according to new data presented at the 84th Annual Meeting of the American Thyroid Association.

“We found and assessed the role of a LincRNA that might play a role in thyroid function and papillary thyroid cancer progression,” study investigator Carmelo Nucera, MD, PhD, an assistant professor at Harvard Medical School in Boston, said in an interview. “This evidence is important because it could provide a novel biomarker to assess in patients with thyroid cancer.”

In recent years, LincRNAs have emerged as key regulators of diverse cellular processes. However, there is still little published data on the function of individual LincRNAs. Significant advances are now occurring in RNA sequencing, and this may pave the way for an unprecedented analysis of these transcripts. 

Robert Smallridge, MD, President-Elect of the American Thyroid Association, said the identification of new circulating markers should improve both the diagnosis and longitudinal follow-up of patients with PTC, if the findings are validated.

Scientists have recently recognized that LincRNAs function in various aspects of cell biology, which has led to increasing attention on their potential role in thyroid disease etiology. For instance, a handful of studies have implicated LincRNAs in a variety of disease states, including oncogenesis.

Experts in this area say LincRNAs could potentially help with earlier diagnosis of PTC in patients who have the BRAFV600E mutation — the most common genetic alteration in patients with the disease that is also associated with poorer prognosis and resistance to radioiodine therapy.

Nucera and colleagues evaluated the LincRNA in an experimental model of PTC harboring the BRAFV600E mutation. LincRNA expression was validated using gene multiprofiling quantitative real-time polymerase chain reaction (RT-PCR) in five normal thyroid tissues, five PTCs with BRAFV600E and two primary normal thyroid and four PTC cell cultures.

Preliminary data indicate that the LincRNA in the TPO gene (TPO-LincRNA), which is specifically associated with thyroid tissue, showed 4.6 mRNA copy number per million copies of 18S rRNA in normal thyroid tissue. In contrast, PTC samples demonstrated a statistically significantly lower copy number of the TPO-LincRNA mRNA expression levels (0.06 mRNA copy number/million copies of 18S rRNA).

Further, TPO mRNA expression levels were significantly lower in the PTCs with BRAFV600E, as compared with normal thyroid tissue samples.

Interestingly, the researchers also found that treatment with vemurafenib, an anti-BRAFV600E therapy, partially rescued the expression of TPO-LincRNA in primary PTC cells with the mutation in vitro when compared with vehicle-treated cells.

“Thyroid cancer is increasing in incidence more than any other cancer, yet the mortality from it is relatively stable. In practice, we are seeing smaller and smaller cancers. Therefore, we need to improve our ability to risk-stratify patients and guide our management based on patients’ prognoses, treating those with more aggressive disease with more aggressive treatment. Knowledge of BRAF mutation status is one tool for doing this,” Carrie Lubitz, MD, MPH, of Massachusetts General Hospital in Boston, told Endocrinology Advisor.

Although there is considerable excitement about this approach and how it may help with staging and guiding therapy among PTC patients with the BRAFV600E mutation, there are still many unanswered questions. Henry Bush, MD, Chair of the Endocrinology Division at Walter Reed National Military Medical Center in Bethesda, Maryland, said it is important that clinicians and their patients are aware that this research is only in its early stages.

“It seems promising but very preliminary and certainly would require additional validation in PTC patients before finding clinical application,” Dr. Bush told Endocrinology Advisor.

Reference

1. Duquette M et al. Oral Abstract 126. Presented at: American Thyroid Association (ATA) 84th Annual Meeting; Oct. 29-Nov. 2, 2014; Coronado, Calif.