Findings from the “Early Onset Prostate Cancer” project, conducted by a collaboration among the German Cancer Research Center, the University of Zurich, Hamburg-Eppendorf University Hospital, Heidelberg University, and many others, show that a key serum biomarker indicates the aggressiveness of prostate cancer. The protein is involved in epigenetic maintenance of tumor cells and is directly associated with prostate cancer malignancy, a central concern to patients and physicians.
It has been known that genetic alterations indicate how dangerous prostate cancer can be but, relative to other cancer types, few mutations exist in prostate tumors. “We therefore suspected that prostate cancer is driven primarily by alterations in epigenetic characteristics, that is, chemical changes in the genetic material that do not affect the sequence of DNA building blocks,” said Professor Christoph Plass, of the German Cancer Research Center, in a press release from the center.
Epigenetic changes refer to DNA modifications beyond those resulting from mutations. Although much is known about the possible types of epigenetic changes, little is known about how cancer cells undergo epigenetic changes of DNA. The group of scientists attempted to resolve this fact and began looking for regulatory proteins involved in epigenetic changes of prostate cancer cells that influence the course of disease.
To begin, the researchers sifted through molecular information from cases of prostate cancer reported in a database and determined that a epigenetic regulatory protein known as BAZ2A is differentially expressed in prostate cancer cells. “The normal function of this protein is to suppress factories that produce cellular proteins and thus affect the viability of cells,” said Professor Roland Elis, of both the German Cancer Research Center and Heidelberg University.
As described in the group’s paper published in Nature Genetics, “BAZ2A (TIP5) Is Involved in Epigenetic Alterations in Prostate Cancer and Its Overexpression Predicts Disease Recurrence,” prostate cancer cells with high levels of BAZ2A were more malignant and able to move around to invade surrounding tissue. The team sought to control BAZ2A expression in hopes to regain control over cancer cell behavior. “[When] we turned off BAZ2A in the cells lines of metastasizing prostate cancer, their growth was paradoxically slowed,” said Professor Elis.
To give the work clinical perspective, the researchers identified nearly 7,700 prostate tumor samples and tested for the presence of BAZ2A. More advanced tumors had higher levels of BAZ2A, and the magnitude related to how advanced and how metastatic the tumors were. “BAZ2A seems to have a direct influence on the aggressiveness of prostate cancer,” said Professor Plass. “This suggests that levels of BAZ2A expression may serve as a valuable predictor of disease progression.”
Work beyond this study will relate more to human patients and the risks they face. “Of course, this still needs to be clinically confirmed,” said Professor Plass. “Particularly in patients whose other clinical results indicate a medium risk, BAZ2A expression may provide important clues for the actual chances of recurrence. This would help physicians and patients choose the most promising treatment.”