Novel Biomarker for Early Prostate Cancer Under Study
Posted: Monday, January 6, 2020
The prostate cancer gene fusion KLK4-KLP1 seems to be a promising early biomarker for prostate cancer, according to genetic research by Nallasivam Palanisamy, PhD, of the Henry Ford Health System, Detroit, and colleagues. KLK4-KLP1 involves the fusion of the androgen-regulated kallikrein-related peptidase 4 (KLK4) protein coding gene and the kallikrein pseudogene 1 (KLKP1). Published in Neoplasia, this research characterizes the gene fusion, suggesting that the KLK4-KLP1 transcript may be detected accurately and reliably in the urine of patients with prostate cancer.
Traditional prostate cancer screening tests rely on the presence of another kallikrein family protease, prostate-specific antigen (PSA), which is not specific to prostate cancer. “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% of high Gleason grade prostate cancer,” said Dr. Palanisamy in a Henry Ford Health System press release. Although KLK4-KLP1 transcripts have also been described in renal cell cancer, a full-length protein is produced only in prostate cancer, they noted.
In this study, the researchers used a combination of methods, including microarray, gene-set enrichment analysis, in situ hybridization, cell culture, and overexpression experiments, as well as other blotting techniques and assays to characterize the expression patterns of the transcript and protein. Of the 659 prostatectomy samples from patients with prostate cancer screened, 32% had detectable KLK4-KLP1 transcripts. The researchers also found that the fusion protein could be detected in needle biopsy samples using a KLK4-KLP1–specific antibody.
“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,” concluded the authors.
Disclosure: The study authors reported no conflicts of interest.