Progress toward development of a simple, noninvasive liquid biopsy test that detects prostate cancer from RNA

Researchers at the Johns Hopkins Kimmel Cancer Center have made significant progress toward development of a simple, noninvasive liquid biopsy test that detects prostate cancer from RNA and other specific metabolic chemicals in the urine.

The investigators emphasize that this is a proof-of-principle study for the urine test, and it must be validated in additional, larger studies before it is ready for clinical use.

The researchers used RNA deep-sequencing and mass spectrometry to identify a previously unknown profile of RNAs and dietary byproducts, known as metabolites, among 126 patients and healthy, normal people. The cohort included 64 patients with prostate cancer, 31 with benign prostatic hyperplasia and prostatitis diseases, and 31 healthy people with none of these conditions. RNA alone was not sufficient to positively identify the cancer, but addition of a group of disease-specific metabolites provided separation of cancer from other diseases and healthy people.

“A simple and noninvasive urine test for prostate cancer would be a significant step forward in diagnosis. Tissue biopsies are invasive and notoriously difficult because they often miss cancer cells, and existing tests, such as PSA (prostate-specific antigen) elevation, are not very helpful in identifying cancer,” says Ranjan Perera, Ph.D., the study’s senior author. Perera is also the director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital, a senior scientist at the Johns Hopkins All Children’s Cancer & Blood Disorders Institute and the Johns Hopkins All Children’s Institute for Fundamental Biomedical Research, and an associate professor of oncology at the Johns Hopkins University School of Medicine and Johns Hopkins Kimmel Cancer Center member.

“We discovered cancer-specific changes in urinary RNAs and metabolites that — if confirmed in a larger, separate group of patients — will allow us to develop a urinary test for prostate cancer in the future,” says Bongyong Lee, Ph.D., the study’s first author and a senior scientist at the Cancer & Blood Disorders Institute.

The urine 37 gene signature distinguishes PCa patients into two groups

rna-seq

(a) Unsupervised clustering of log-fold change (logFC) values shows that patients can be grouped into two groups, Group A and Group B, exhibiting lower and higher expression of the 37 genes compared to the matched normal, respectively. The logFC was obtained from the log2 ratio of RPKM values of tumor and matched normal of the listed genes. (b,c) KEGG pathway analysis suggests that the two molecularly identified groups are physiologically distinct, as shown by opposite enrichment of the depicted pathways. The logFC values were obtained by comparing tumor versus matched normal samples from each group via paired limma analysis.

Source – Johns Hopkins Medicine

Lee B, Mahmud I, Marchica J et al. (2020) Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery. Sci Rep 10, 3716. [article]

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