University of Virginia Health System
Prostate cancer has distinct genetic properties in different groups of men that can be targeted to improve patient outcomes, UVA Cancer Center researchers have discovered. Based on new findings in Chinese men, the researchers are urging similar studies in other groups to advance precision medicine and better tailor treatments.
An international team of researchers co-led by UVA’s Hui Li, PhD, looked at what are known as “chimeric RNA” in Chinese men and found both similarities and differences to those seen in Western men. These RNAs can contribute to the growth of cancer and are widely used as both indicators of cancer and targets for cancer treatment.
By targeting chimeric RNA specific to Chinese men, doctors may be able to develop better, more effective prostate cancer treatments for Chinese patients, Li says. He notes that Asian populations have the highest ratio of prostate cancer deaths to new cases (40%) – higher than in Europe (18%), Northern America (10%) or even worldwide (25%).
But the findings also speak to the potential of the approach for improving cancer care for other groups.
“Prostate cancer is a worldwide problem. It is the most common cancer in men, with clear racial disparities,” said Li, of the University of Virginia School of Medicine’s Department of Pathology. “More than 70 percent of Asian prostate cancer patients are in the intermediate or advanced stage at the first diagnosis. They are more prone to metastasis and drug resistance, which is consistent with a 5-year survival rate of less than 30percent. Our findings may not only explain the racial disparity, but provide some handles we can use to tackle the disease.”
Chimeras in Cancer
Chimeric RNA combines operating instructions from two or more different genes; these fusions are found in both healthy cells and cancerous ones. In cancer, they can influence tumor formation and growth by producing particular proteins, for example, or by altering gene activity.
To better understand chimeric RNA in a specific patient population, Li and his team analyzed data from the Cancer Genome Atlas and the Chinese Prostate Cancer Genome and Epigenome Atlas. They found that Chinese men had several distinct chimeric RNA patterns, including in cancer epithelial cells as well as in macrophages and T cells, immune cells found in and around tumors.
The scientists then discovered how the chimeric RNA drive tumor growth and reshape cellular communications surrounding the tumors. They also revealed how the chimeras contribute to the activity of stromal cells that play a crucial role in cancer’s formation and progression.
“This is the first comparison between two prostate cancer populations focusing on chimeric RNAs,” Li said. “It is also the first study to examine chimeric RNAs in different cell types within cancer.”
Precise Prostate Cancer Treatment
The new findings offer important insights into how prostate cancer develops in Chinese men. But the scientists also use their new paper outlining the discovery to highlight the potential of the approach to benefit all patients. By better understanding how chimeric RNA differs in various populations, doctors can target these distinct RNA profiles to develop more tailored – and more effective – prostate cancer treatments.
Further, chimeric RNA isn’t just found in prostate cancer but in cancer generally. So the approach could open doors in the battle against many forms of the disease.
“We were able to validate over 100 chimeric RNAs, the largest list in the field, with some having clear diagnostic and prognostic potential,” Li said. “In addition, we have identified multiple chimeric RNAs that influence prostate cancer or tumor microenvironment, which contribute to the tumorigenesis [tumor formation]. Chimeric RNAs as such represent a hidden repertoire for biomarkers and/or therapeutic targets.”
Findings Published
The researchers have published their findings in the scientific journal iMeta. The paper is open access, meaning it is free to read. The research team consisted of Qiong Wang, Shunli Yu, Jirong Jie, Justin Elfman, Zhi Xiong, Sandeep Singh, Samir Lalani, Yiwei Wang, Kaiwen Li, Bisheng Cheng, Ze Gao, Xu Gao, Hui Li and Hai Huang. The researchers have no financial interest in the work.
“Prostate cancer is a worldwide problem. It is the most common cancer in men, with clear racial disparities,” said researcher Hui Li, PhD, of the University of Virginia School of Medicine’s Department of Pathology. “More than 70 percent of Asian prostate cancer patients are in the intermediate or advanced stage at the first diagnosis. They are more prone to metastasis and drug resistance, which is consistent with a 5-year survival rate of less than 30 percent. Our findings may not only explain the racial disparity, but provide some handles we can use to tackle the disease.”
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