Oncology/Hematology
Biomarkers Tied to Recurrent Thyroid Cancer
Published: Oct 28, 2013 | Updated: Oct 28, 2013
A pair of microRNA (miRNA) biomarkers were strong predictors of papillary thyroid cancer (PTC) recurrence, according to researchers.
MicroRNA-222 and microRNA-146b were overexpressed 10.8-fold and 8.9-fold in the tissue samples of patients with recurrent PTC compared with samples from patients who did not recur (P=0.014 and P=0.038, respectively), reported James C. Lee, FRACS, of the Kolling Institute for Medical Research in St. Leonards, Australia, and colleagues.
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.After the PTC group underwent total thyroidectomy, the biomarkers decreased 2.7-fold and 5.1-fold, respectively (P=0.03 for both), in patient plasma draws, they added.
Both miRNAs were also elevated in plasma of another subset of patients with multinodular goiter, and decreased after total thyroidectomy.
This study is the largest comparing pre- and postoperative plasma miRNA levels in patients with PTC, and the first to include patients with multinodular goiter, the authors pointed out.
However, the results suggest the presence of these biomarkers in plasma might not be useful in diagnosing new cases of PTC, because they don't appear to distinguish between malignant and benign follicular growth, they cautioned.
PTC is the most common endocrine malignancy, and its incidence has been on the rise over the past few decades. For most patients, the prognosis is good, with more than 90% surviving to at least 10 years. However, up to 30% of patients recur at that point, and predicting that recurrence has been a challenge.
Specific biomarkers indicating disease aggressiveness, or likelihood of recurrence, would allow aggressive adjuvant therapy or more rigorous surveillance for these cohorts, while sparing other patients unnecessary treatment and surveillance.
Previous researchers have reported that they have been able to measure miRNA levels in fine-needle aspiration samples.
"If differential levels of recurrence-associated miRNAs can be demonstrated in fine-needle aspiration samples, then even surgical decisions, such as the extent of lymph node dissection, may be guided by miRNA levels," Lee's group wrote.
A number of molecular markers for severity of disease and recurrence have been investigated, including the BRAF mutation, p27, p21, cyclin D1, CEACAM-1, osteopnton and E-cadheren. "However, to date, none have reached the stage of clinical application," the authors said.
The researchers used archival tissue samples from patients who had recurred with PTC and patients who had not recurred for the first part of the study. For the second, they recruited healthy volunteers, as well as patients newly diagnosed with PTC or multinodular goiter who were scheduled to undergo total thyroidectomy.
Blood samples were drawn both pre-and postoperatively for the patients who underwent surgery.
According to the results, miRNA-222 and miRNA-146b were associated with the presence of the BRAF mutation, suggesting that these biomarkers may be part of an oncogenic signature associated with more aggressive disease.
A previous study reported miRNA-146b and miRNA-222 over-expressed in aggressive PTC, and an in vitro study found that miRNA-146b overexpression increased cell migration and invasion, as well as resistance to chemotherapy-induced apoptosis.
Although these results are promising, the authors said larger, longitudinal studies are need to confirm the potential of these two miRNAs as surveillance tools and as indicators of the severity of disease.
Further in vitro studies are also required "to clarify the mechanism of action of these miRNAs within PTC tissue in the context of recurrence as well as their mechanism of secretion into, and functions within, the circulation," they concluded.
This research was partly funded by an institutional cancer grant to the University of Sydney. Lee was the recipient of the Neville Brown Scholarship and Australian Postgraduate Award in 2012.
The authors reported no conflicts of interest.
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