New interdisciplinary research lays groundwork for predicting if bone cancer will spread

New interdisciplinary research is exploring the probability of tumors metastasizing, or spreading in patients with osteosarcoma, a bone cancer in which children and adolescents make up approximately half of all diagnosed cases. Early evidence suggests that certain epigenetic markers and gene expression profiles could indicate whether a tumor is likely to metastasize, even at early stages before traditional methods can detect such risks. This study provides a promising pathway for earlier predictions of metastatic potential, which could enable targeted interventions for patients with osteosarcoma—a rare type of cancer that starts in the bones.

Irtisha Singh, PhD, associate professor at the Texas A&M University College of Medicine, and Jason T. Yustein, MD, PhD, professor at the Winship Cancer Institute and the Aflac Cancer and Blood Disorders Center at Emory University, combined their expertise to examine osteosarcoma at the cellular level.

Each person, Singh said, has a set of genes that all provide different levels of gene expression, causing different cells in different people to behave differently. “The cells in your eyes versus the cells in your skin and lungs and every different part of the body are doing very different things, which means that although they have the same DNA, they are expressing a very different set of genes,” she said.

Through this research, Singh and Yustein aim to uncover why some cells become cancerous and metastasize, while others do not, even if they turn cancerous. The team believes that epigenetic markers—factors that influence gene expression—play a key role in how cancer behaves. Dysregulation of cells, driven by these epigenetic changes, appears to underlie this behavior.

Osteosarcoma presents particular challenges, Singh said, because it largely occurs in those under 18 years of age, with children and teens accounting for approximately half of diagnosed cases. Early-age diagnosis limits treatment options due to risks of inhibiting growth and development, heightening the need for early intervention, especially in younger patients.

Yustein saw osteosarcoma patients at the clinic in Atlanta, Singh said. All these patients had the sarcoma surgically removed. However, a subgroup of them experienced metastasis of their cancer, despite surgical intervention, spurring Yustein to examine samples at the most basic level.

“He took these biopsies and created patient-derived xenografts, and then we went ahead and did some epigenetic profiling and gene expression profiling of these samples,” Singh said. “Then we compared to see if we see some fundamental changes in the two groups of patients.”

The team found that the epigenetic state of cells, DNA, RNA and chromatin play a strong role in determining gene expression, and therefore probability of tumor metastasis. Singh explained that while DNA is mostly the same in all cells, whether a gene is “turned on” depends on how the DNA is packed. When DNA is tightly wrapped around proteins called nucleosomes, the genes stay off. But if the DNA has certain chemical changes—called epigenetic changes—it becomes looser and easier to read.

These changes make it possible for the cell to turn those genes on and make RNA from them. The RNA allows the gene to be expressed and is what causes some tumor cells to metastasize. The changes within these cells make them fundamentally different from other tumors that do not metastasize, which could make it possible for practitioners to someday predict metastasis before it happens.

“I think the key highlight for me for this research was that normally the way we think about cancer, especially the ones that metastasize, is that you have the same kind of cancer across patients and then somehow certain cells gain these special abilities to move away from the primary site, and that's when metastasis happens,” she said.

“But from this research, what really came out was that at the fundamental level itself, the primary tumors itself are very different, so maybe even ahead of time you can tell that these patients will undergo metastasis versus not.”

Symptoms of osteosarcoma may include joint pain, bone pain and bone swelling. Although children and teens account for approximately half of diagnosed cases, any age can develop osteosarcoma, and the United States sees roughly a thousand new diagnoses annually. Unlike other cancers, osteosarcoma survival rates have not improved in the past 20 years, making more research vital, Singh said, adding that osteosarcoma research may be expanded by examining other types of sarcomas, like rhabdomyosarcoma—a cancer closely related to osteosarcoma.

By Laura Tolentino, Texas A&M Health

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