This urine analysis might also be able to detect advanced prostate tumors. The researchers found that the subset of 37 upregulated genes could divide the cancerous samples into 2 distinct groups: A and B, with group B expressing significantly higher levels of PCA3. Higher expression of this marker has been linked to higher tumor aggressiveness,3 and its upregulation occurred despite similarities in tumor stage, Gleason score, and metastasis status between the 2 groups.

The urine analysis also revealed possible novel drug targets for prostate cancer. One of the metabolites that was highly increased in cancerous urine samples was glutamate oxaloacetate transaminase 1 (GOT1), an enzyme the authors found to be the main metabolite influencing alanine, aspartic acid, and glutamic acid metabolism, as well as the TCA cycle — both of which are critical for rapid division in cancer cells.

GOT1 was highly expressed in malignant prostate tumors. The authors also found abnormal levels of glutamate, the product of GOT1, in primary and metastatic prostate cancer samples compared with levels found in normal tissues. When the researchers knocked down GOT1 in the cancer cell lines LNCaP and PC3 using siRNA, they observed increased cell death in both, indicating that GOT1 could be a molecular target that could be manipulated in efforts to eliminate prostate cancer cells.

The results are encouraging, as they show the promise of unveiling cancer-specific changes using a noninvasive approach and identify pathways researchers can pursue to try to stop tumor growth — but a larger study is needed. “Further validation is always requisite in these types of analyses,” Dr Shore said. “If [the researchers are] able to further correlate and reproduce their findings, that would be of great value clinically.” Dr Perera emphasized that this is just the beginning: “If we wanted to use this as a test, we have to do large-scale clinical trials. That’s something that we are thinking about doing.”

Jeffrey R. Smith, MD, PhD, professor of medicine at Vanderbilt Medical University, Nashville, Tennessee, who was not involved in the study, agreed that the study results need to be reproducible. “This study nominates a biomarker signature using 2 powerful research approaches, but independent replication of the observations is a key next step,” he said. He pointed out that although the test seems to accurately distinguish between normal and prostate cancer samples, the authors must be able to replicate those findings in entirely independent data — for example, in the context of a prospective clinical screening trial. “Validation and establishment of sensitivity and specificity within a very well-powered independent sample is a logical next step,” Smith added.

The results of this study have been met with enthusiasm from patients who could possibly benefit from the use of such a test. “There are a lot of inquiries I’m getting right now of people telling me that they have prostate cancer, and they want to know when this test is going to be available,” said Dr Perera. “When I say that we have to do a bigger study, they ask if they can enroll in it.” But for now, the major barrier is study funding. Dr Perera is currently exploring industry collaborations to initiate a larger clinical trial.

References

  1.  Lee B, Mahmud I, Marchica J, et al. Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery. Sci Rep. 2020;10(1):3716.
  2.  Truong M, Yang B, Jarrard DF. Toward the detection of prostate cancer in urine: a critical analysis. J Urol. 2013;189(2):422-429.
  3. Merola R, Tomao L, Antenucci A, et al. PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience. J Exp Clin Cancer Res. 2015;34:15.