A non-invasive prostate cancer screening test uses a unique biomarker that can be detected in urine samples of patients.
Prostate cancer is the second most frequently diagnosed cancer in men and is the fifth leading cause of death worldwide. In 2018, prostate cancer diagnoses accounted for 7.1 % of all cancers diagnosed worldwide. The risk of prostate cancer is higher in men above 65 years of age. While prostate cancer is a serious disease, most men diagnosed do not die from it. Survival rates range from 98 % in the USA to approximately 83 % in the EU and 76 % in the eastern countries. The higher survival rates could be attributed to the slow progression of the disease in the majority of cases, which increases the odds of early diagnosis during regular screenings.
Screening for prostate cancer involves testing for the prostate-specific antigen (PSA), which is a protein made by the cells in the prostate gland. High PSA levels correlate with higher chances of having prostate cancer. However, PSA levels can be raised due to many factors other than cancer, making PSA levels an inadequate diagnostic marker for prostate cancer. When a person is found to have high levels of PSA, a prostate biopsy, which is an invasive procedure, is usually conducted to confirm the diagnosis of prostate cancer. These limitations of current diagnostic methods and the different molecular mechanisms underpinning this disease suggest the need for unique and easily detectable biomarkers for prostate cancer.
Biomarker found that can be detected in urine samples
A research study published in Neoplasia identifies one such unique biomarker that can be detected in urine sample of patients. This biomarker is formed by the gene fusion of two genes: the protein coding gene KLK4 and the pseudogene KLKP1. This gene fusion results in a protein product that can be detected in urine samples and also in needle biopsy tissue samples. The researchers also determined that the KLK4-KLKP1 fusion is specific to prostate tissue and is cancer-specific.
Biomarker involved in the growth of prostate cancer
The researchers conducted a series of experiments and found that the fusion gene may be involved in prostate cancer development, as it promoted the growth, invasion, and tumor formation in non-cancerous epithelial cells. As explained by Dr. Palanisamy, the lead researcher of the study, “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 ad a therapeutic target.” The research was carried out at the Vattikuti Urology Institute at the Henry Ford Health System, Detroit, USA.
The study involved screening a cohort of 659 patients that included 250 African-American men. The significant representation of African-American men in the study is important as they are at higher risk of developing prostate cancer. The fusion gene KLK4-KLKP1 was detected in 32 % of the prostate cancer patients.
The detection of unique biomarkers can help to stratify patients on the basis of the underlying molecular mechanisms. Prostate cancer is recognized to be a complex disease with variation in the genetic underpinnings, which in turn is linked to differences in outcomes and disease progression. Patient stratification based on the genetic differences in the causal mechanism can facilitate more precisely targeted therapy. As noted by Dr. Craig Rogers, M.D, chair of the Vattikuti Urology Institute at Henry Ford Health System, “The differences of new biomarkers ultimately benefits our patients, as it advances our understanding of this complex disease and how to most effectively treat it.”
Written by Bhavana Achary, Ph.D
Chakravarthi BV, Dedigama-Arachchige P, Carskadon S, Sundaram SK, Li J, Wu KH, Chandrashekar DS, Peabody JO, Stricker H, Hwang C, Chitale DA, Williamson SR, Gupta NS, Navone NM, Rogers C, Menon M, Varambally S, Palanisamy N. Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer. Neoplasia. 2019 Aug 22;21(10):989-1002
Press release retrieved from https://www.eurekalert.org/pub_releases/2019-10/hfhs-sbi100219.php
Prevalence of prostate cancer – Rawla P. (2019). Epidemiology of Prostate Cancer. World journal of oncology, 10(2), 63–89.
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