Identifying kidney cancer and differentiating between kidney cancer tumor types with a urine test is still more of a fond wish than a reality, but several strategies that are in late-stage development offer promise for screening, diagnosis, prognosis, and evaluation of drug response for patients with kidney lesions.
For example, detection of truncated proteins in urine can be used to differentiate benign lesions, such as renal oncocytomas, from renal cell carcinomas (RCCs), said Barbara Köditz, a PhD candidate at University Hospital Cologne, in Cologne, Germany.
These proteins can be identified using a simple, cheap lateral flow assay rather than a more time-consuming and costly enzyme-linked immunosorbent assay (ELISA).
Köditz was speaking at a narrated poster presentation during the recent European Association of Urology 2021 Annual Meeting (EAU 2021).
Her group had previously shown that two truncated proteins ― proteins that are shorter but biologically active versions of the parent protein ― were differentially expressed in kidney lesions. The protein Mxi-2, regulated by a microRNA (miRNA) labeled 15a, was overexpressed in RCC, and Vim3, regulated by miRNA 498, was overexpressed in oncocytomas.
Mxi-2 is a truncated variant of MAP kinase P38. Vim3 is a truncated variant of vimentin.
“We asked the question if these markers can be used as a noninvasive biomarker in urine,” she said.
They examined 350 urine samples from a biobank using ELISA to determine expression of Mxi-2 and Vim3, and they used quantitative real-time polymerase chain reactions to detect miRNAs associated with small renal masses.
They found that Vim3 expression was significantly elevated in samples from patients with oncocytomas compared to all histologic subtypes of RCC, including chromophobe, papillary, and clear-cell RCC (P < .0001), whereas Mxi-2 was predominantly overexpressed in clear-cell RCC (P < .0001).
The lateral flow assay that the investigators developed showed good specificity, Köditz said, although she did not present data regarding this.
Köditz and colleagues also analyzed presurgical samples from 45 patients with small renal masses to see whether their urine test could differentiate cancer subtypes. They found that miRNA 15a/Mxi-2 overexpression was detectable in samples from patients with clear-cell and chromophobe RCC, whereas miRNA 498/Vim 3 were predominantly overexpressed in samples from patients with oncocytomas.
Other Biomarker Candidates
“I was really surprised that we have some markers in urine, because when I started my research 30 years ago, I learned that it doesn’t make sense to look for anything in urine, because the tumors have no contact to urine,” Kerstin Junker, MD, PhD, from Saarland University, Homburg, Germany, commented during the meeting.
Since then, investigators have discovered that although cells from renal cell tumors have minimal contact with the urinary system, they can be detected after they are released into circulation and are filtered through the kidney into urine, she said.
In a review of current biomarker research, also presented at EAU 2021, Junker said that several other miRNAs are being explored, alone and in combination, for their potential in kidney cancer screening.
She noted that in addition to miRNAs, combinations of proteomic markers hold promise for differentiating small renal masses.
“In my view, the differentiation between benign and malign lesions is the most relevant task for urinary biomarkers in kidney cancer, especially in small renal masses. The prognostic role of urinary markers has to be tested in further studies, especially in comparison to blood-based markers. In contrast, predictive biomarkers for systemic therapy of metastatic disease should be investigated in serum or plasma instead of in urinary markers,” she said.
A High Bar
Jack A Schalken, PhD, from Radboud University, Nijmegen, the Netherlands, who moderated the session in which Junker presented her talk, commented that urinary biomarkers are not yet ready for prime time, but should be.
“Apparently, we are putting the bar extremely high for the new biomarkers. If we would have done that for prostate-specific antigen (PSA), we would never have used PSA,” he said.
“I still think that the urologist community at large is still somewhat biomarker skeptic, so I would strongly urge that we start using them rather than keep saying that they’re not perfect yet, because in cancer research, nothing is perfect,” he said.
No source of funding for the study was reported. Köditz, Junker, and Schalken have disclosed no relevant financial relationships.
European Association of Urology 2021 Annual Meeting (EAU 2021): Abstract PO533. Presented July 10, 2021.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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