A new study from Wake Forest Baptist Medical Center is the first to report that high blood calcium levels might predict ovarian cancer, the most fatal of the gynecologic cancers.
Lead author Gary G. Schwartz, Ph.D., a cancer epidemiologist at Wake Forest Baptist, and colleague, Halcyon G. Skinner, Ph.D., of the University of Wisconsin Carbone Cancer Center, examined associations between blood calcium and ovarian cancer in two national population-based groups. They found that women who were later diagnosed with ovarian cancer and women who later died of ovarian cancer had higher levels of calcium in blood than women who did not before their cancer diagnosis.
Schwartz, who is well-known for his epidemiologic research in prostate cancer, said the idea for this study came about because of published research from his group which showed that men whose calcium levels were higher than normal have an increased risk of fatal prostate cancer. That led him to wonder if a similar relationship were true of ovarian cancer.
“One approach to cancer biomarker discovery is to identify a factor that is differentially expressed in individuals with and without cancer and to examine that factor’s ability to detect cancer in an independent sample of individuals,” Schwartz said. “Everyone’s got calcium and the body regulates it very tightly,” Skinner added. “We know that some rare forms of ovarian cancer are associated with very high calcium, so it’s worth considering whether more common ovarian cancers are associated with moderately high calcium.”
The idea is plausible, Schwartz explained, because many ovarian cancers express increased levels of a protein, parathyroid hormone-related protein (PTRHrP), which is known to raise calcium levels in blood in many other cancers.
Ovarian cancer has a high fatality rate because it is hard to detect and by the time symptoms arise, the cancer is usually advanced. Schwartz said early diagnosis might be accomplished through the use of a calcium biomarker, but cautions that more research is needed to confirm these results. “We found the link between serum calcium and ovarian cancer; we confirmed it, and even though the study is small, we’re reporting it because it’s a very simple thing in theory to test.”
Cell stiffness may predict ovarian cancer metastasis
Cell stiffness may be a useful biomarker for evaluating the relative metastatic potential of ovarian and perhaps other types of cancer cells, a recent study indicates.
“In order to spread, metastatic cells must push themselves into the bloodstream. As a result, they must be highly deformable and softer,” explained investigator Todd Sulchek, a faculty member of the George W. Woodruff School of Mechanical Engineering at Georgia Institute of Technology in Atlanta, in a statement issued by the facility.
As Sulchek and his research partners noted in their report for PLoS One, the metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. The group, which included members with a molecular cancer laboratory on the campus, used a process called atomic force microscopy to study the mechanical properties of various ovarian cell lines. A soft mechanical probe made contact with healthy, malignant, and metastatic ovarian cells to measure their stiffness.
The investigators demonstrated that consistent with previous studies conducted in other types of epithelial cancer, ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than do nonmalignant ovarian epithelial cells. A detailed examination of highly invasive ovarian cancer cells relative to their less invasive parental cells revealed that deformability is also an accurate biomarker of metastatic potential.
Knowing that highly metastatic ovarian cancer cells are several times softer than less metastatic ovarian cancer cells can provide clinicians with a valuable clue as they search for cancerous cells and attempt to administer treatment to destroy them. Sulchek’s team predicts that when their technology is further developed, it could be used to design optimal chemotherapies for women with ovarian cancer as well as patients with other types of cancer.
Delicia Honen Yard
The study is published online this month in the journal Gynecologic Oncology. The research was supported by the Comprehensive Cancer Center of Wake Forest and the UW School of Medicine and Public Health.
Most ovarian cancers are diagnosed when the disease is already in an advanced stage, i.e. stage III and IV. Physicians surgically remove as much of the tumor as possible, before administering platinum-based chemotherapy. However, the tools to predict how an ovarian cancer patient responds to platinum-based chemotherapy still remain inadequate.
Josephine Kang, M.D., Ph.D., of the Department of Radiation Oncology at the Dana Farber Cancer Institute, and her team wanted to establish whether a DNA repair pathway-focused score could help to predict outcomes for ovarian cancer patients who are treated with platinum-based chemotherapy.
The Cancer Genome Atlas database (TCGA) provided gene expression data of patients with advanced stage ovarian cancer, and the team developed a molecular score by examining the genes involved in platinum-induced DNA damage repair pathways. The patients were categorized into either low or high score categories, and the team assessed the score’s prognostic value for overall survival, recurrence free survival, and progression-free survival.
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