“Translational research, from bench to bedside,” is how Dr. Paul G. Walfish describes recent work conducted in his lab, which has led to the discovery of an intracellular biomarker and its use in identifying aggressive thyroid cancer.
Walfish, an emeritus professor at U of T’s Faculty of Medicine and researcher at Mt. Sinai Hospital, is the senior author of the study published this June in the journal BMC Cancer. His research team included U of T and Mt. Sinai affiliated scientists Dr. Ranju Ralhan, Jun Cao, Terence Lim, Dr. Christina MacMillan, and Dr. Jeremy L. Freeman.
The research is clinically applicable, with results that may be seen in the short term and has the potential to assist medical practitioners in predicting patient survival outcomes and improving the diagnosis of thyroid cancers.
Thyroid cancers are a disorder of the thyroid gland, a small but important endocrine gland located just below the adam’s apple in humans. The thyroid releases hormones involved in maintaining heart rate, body temperature, and metabolism. While the rates of thyroid cancers were previously underestimated, they are now known to be more prevalent than the medical community initially believed, thanks to new techniques used to identify them. Thyroid cancers tend to occur more frequently in women, and their cause is similar to that of any cancer: cells mutate and become cancerous when they lose their ability to regulate and control division.
Walfish’s research team looked at archived thyroid cancer tissue samples from patients and found that in cases of aggressive thyroid cancer, increased levels of the biomarker Ep-ICD were found in the nucleus and cytoplasm of thyroid cells. In cases of low-grade papillary thyroid cancers — a less severe class of thyroid cancers associated with a much more positive prognosis — Ep-ICD levels were virtually undetectable. According to the published article, Ep-ICD levels in the nucleus of thyroid cells “may serve as a useful biomarker for aggressive thyroid cancer and may represent a novel diagnostic, prognostic and therapeutic target.”
Ep-ICD is formed from a precursor protein in the cell membrane called Ep-CAM, which eventually gets cleaved and relocates to the nucleus of the cell to form Ep-ICD. Although this pathway is well understood, the reasons for the association between elevated Ep-ICD and aggressive thyroid cancers are unclear and potentially the subject of future research. For Walfish’s team, future areas of study will involve defining the degrees of aggressiveness of thyroid cancer, including how closely Ep-ICD levels can match gradients of thyroid cancer severity.
Perhaps the most noteworthy feature of the study is just how “striking the correlation is between life expectancy and chemical marker levels,” Walfish remarks. The correlation between nuclear Ep-ICD levels and the reduction in overall survival time in thyroid cancer patients was astonishingly strong. Over 10 years of average survival time separated the high and low Ep-ICD patient categories.
Correlating the levels of certain biomarkers to the severity of a cancer is a concept that can be applied not only to thyroid cancers but potentially to every cancer. Walfish’s team is indeed “in the process of investigating whether similar mechanisms occur in other epithelial cancers,” hoping to find results as compelling as those from this study.
