Cancer cells are known to have short telomeres, but just how short they are from cancer cell to cancer cell may be a determining factor in a prostate cancer patient's prognosis, according to a study led by Johns Hopkins scientists.
"Doctors are looking for new ways to accurately predict prostate cancer patients' prognoses, because the current methods that use disease stage, Gleason score, and PSA are not perfect," says Alan Meeker, Ph.D., assistant professor of pathology at The Johns Hopkins University School of Medicine and its Kimmel Cancer Center. "Telomere shortening is common in cancer, but the degree of shortening varies from one cancer cell to another within each patient, and this variability may give us a better idea of how prostate cancers behave."
In the study, described in the October issue of Cancer Discovery, the scientists studied tissue samples from 596 men surgically treated for prostate cancer thought to be confined to the prostate and who were participants in a long-term follow-up study on men's health. Then, they used images of prostate cancer cells and nearby cells called stroma, which include smooth muscle and fibroblast cells, taken from surgery-tissue samples of each patient.
Meeker and his team used a technique they developed called telomere-specific fluorescent in situ hybridization (TELI-FISH) to measure telomere length in cancer and stromal cells. The technique uses fluorescent-labeled probes specific for particular locations in DNA, and is commonly used to detect or confirm gene or chromosome abnormalities. In the new study, a fluorescent probe specific for telomere regions was added to the cells, enabling the scientists to identify these specific chromosomal locations under a microscope and measure the level of fluorescence that corresponds to telomere length.
After determining telomere length for more than 40,000 cells among the samples, disease-pattern experts at Johns Hopkins then correlated telomere length measurements in the cancer and stromal cells with each patient's survival.
"Men who had a combination of more variable telomere length among cancer cells and shorter telomere length in stromal cells were more likely to develop metastatic disease and die sooner from their prostate cancer than other men," says Elizabeth Platz, Sc.D., M.P.H., professor of epidemiology at The Johns Hopkins Bloomberg School of Public Health and the Martin D. Abeloff Scholar in Cancer Prevention at the Johns Hopkins Kimmel Cancer Center.
In the group of 98 men with more variable telomere length in cancer cells and shorter telomeres in stromal cells, 20 died of their prostate cancer an average of 8.4 years after diagnosis. Accounting for standard prognostic factors, these men were 14 times more likely to die of their prostate cancer compared with another group of 98 men whose telomeres had less variable length among cancer cells and were longer in stromal cells. In this group, only one man died, and that was after 16.5 years.
"Our studies strongly suggest that the combination of telomere length in stromal cells and its variability among prostate cancer cells could be a marker for prostate cancer prognosis," says Platz.
Meeker and Platz are continuing to study additional groups of patients and are now using an automated fluorescence microscope and computer software to speed the collection of tissue images and extract telomere data.
Funding for the study was provided by the Department of Defense, the National Institutes of Health's National Cancer Institute (CA58236, CA55075, CA72036, CA133891, CA141298) and National Heart, Lung, and Blood Institute (HL35464), the Seraph Foundation, and the Prostate Cancer Foundation.
Tissue samples used for the study were taken from men enrolled in Harvard's Health Professionals Follow-Up Study.
Scientists contributing to the research include Christopher M. Heaphy, Ghil Suk Yoon, Sarah B. Peskoe, Corinne E. Joshu, Thomas K. Lee, Jessica L. Hicks, and Angelo M. De Marzo at Johns Hopkins; and Edward Giovannucci, Stacey A. Kenfield, Lorelei A. Mucci, and Meir J. Stampfer at Harvard School of Public Health.
JOHNS HOPKINS MEDICINE
Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's mission is to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, more than 38 primary health care outpatient sites and other businesses that care for national and international patients and activities. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation for 21 years by U.S. News & World Report.Johns Hopkins Kimmel Cancer Center
Vanessa Wasta | EurekAlert!
UC San Diego researchers develop sensors to detect and measure cancer's ability to spread
06.12.2018 | University of California - San Diego
New cancer immunotherapy approach turns immune cells into tiny anti-tumor drug factories
05.12.2018 | University of California - San Diego
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals
Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.
Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.
Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...
Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.
The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.
06.12.2018 | Event News
03.12.2018 | Event News
28.11.2018 | Event News
07.12.2018 | Life Sciences
07.12.2018 | Materials Sciences
07.12.2018 | Physics and Astronomy