A research study published in Neoplasia, led by lead researcher Nallasivam Palanisamy, Ph.D., associate researcher at the Vattikuti Urology Institute at Henry Ford Health System, identified a novel fusion of the prostate cancer gene involving the KLK4 protein coding gene and KLKP1 pseudogene. In urine samples of prostate cancer patients, this particular biomarker can be identified, providing a non-invasive method of detection.
The prostate-specific antigen (PSA) test is currently being used as the standard method of screening prostate cancer. Nevertheless, elevated levels of PSA are not exclusive to prostate cancer, as benign prostate conditions can also induce them. As a consequence, an elevated PSA test can sometimes result in the patient undergoing an unnecessary prostate biopsy that carries a risk of bleeding and infection. Results from this work can provide a more accurate and reliable approach for diagnosing prostate cancer.
“This study is exciting because it has the potential to offer a non-invasive alternative to the traditional PSA test in order to diagnose significant prostate cancers,” said Craig Rogers, M.D., chair of the Vattikuti Urology Institute at Henry Ford Health System. “The discovery of new biomarkers ultimately benefits our patients, as it advances our understanding of this complex disease and how to most effectively treat it.”
When the KLK4 protein coding gene and KLKP1 pseudogene fuse together, the fusion gene KLK4-KLKP1 is formed. Pseudogenes like KLKP1 are the non-functional, or dead, versions of an actual gene that is normally not expressed in a cell but can become active in cancerous cells and disrupt the functions of the actual gene.
“The unique feature of this fusion gene is the conversion of the noncoding pseudogene KLKP1 into a protein coding gene, and its unique expression in about 30 percent of high Gleason grade prostate cancer,” said Dr. Palanisamy. “Like other ETS family gene fusions, KLK4-KLKP1 can also be detected in the urine samples of patients with prostate cancer, enabling non-invasive detection of prostate cancer. Given the unique feature of this fusion, prostate cancer specific expression, oncogenic properties and noninvasive detection, this novel gene fusion has the potential to be used as a biomarker for early detection of prostate cancer and a therapeutic target.”
A cohort of 659 patients (380 White American; 250 African American, and 29 patients of other races) were screened by the researchers conducting this analysis, which revealed that the KLK4-KLKP1 fusion gene is expressed in about 32 percent of patients with prostate cancer, representing a distinct subset of cases of prostate cancer. Correlative research has shown that the new gene for fusion can be used for cancer detection in conjunction with other molecular markers for prostate cancer. In addition to urine samples, a particular antibody could also be used to detect the fusion in needle biopsy tissue samples.
Prostate cancer in the United States is the most common cancer among men. Advances in diagnosis, care, and management have resulted in increased rates of survival, but prostate cancer remains among American men the second leading cause of cancer-related deaths. The underlying molecular nature of the disease itself is one of the main obstacles to effective prostate cancer regulation.
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