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EAU 2021 | miR-371a-3p as a biomarker in testicular cancer

Matthew Murray, MB, BChir, PhD, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, talks on the role of microRNA (miRNA) as a biomarker in germ cell tumors, in particular for patients with testicular cancer. Dr Murray describes how the miRNA-371~373 and miRNA-302/367 clusters are highly overexpressed in all malignant germ cell tumors and comments on the impacts of this discovery. Dr Murray reports that detection of one miRNA from patient blood samples, miR-371a-3p, can be used as a biomarker for response to treatment in patients with testicular cancer. This interview took place at the European Association of Urology (EAU) Virtual Meeting 2021.

Transcript (edited for clarity)

About a decade ago, around 2010 or 11, we identified that there is a panel of short non-protein coding RNAs termed micro-RNAs in two specific clusters that are over expressed in all malignant germ cell tumors, of which testicular cancer is the most common type. And those two micro-RNA clusters are miR-371~3 and miR-302/367. And over the intervening 10 years, what’s been shown is not only are those micro-RNAs at very high levels in the tumors themselves when compared to normal control samples, but those levels also very high in patient blood stream at the time of diagnosis...

About a decade ago, around 2010 or 11, we identified that there is a panel of short non-protein coding RNAs termed micro-RNAs in two specific clusters that are over expressed in all malignant germ cell tumors, of which testicular cancer is the most common type. And those two micro-RNA clusters are miR-371~3 and miR-302/367. And over the intervening 10 years, what’s been shown is not only are those micro-RNAs at very high levels in the tumors themselves when compared to normal control samples, but those levels also very high in patient blood stream at the time of diagnosis.

So, over time, what we’ve narrowed down is from micro-RNAs from those two clusters, we initially identified eight that were very high. That was then narrowed down to a panel of four. And more recent work has shown that just one micro-RNA, termed microRNA-371a-3p, is very high at patient diagnosis, falls with treatment. So, for patients who have localized disease to the testes, and the affected testis is removed, within a few days, however high the level is at diagnosis, the level is returned to normal. For patients who have got metastatic disease and need chemotherapy, the levels fall with chemotherapy and remain low in uneventful clinical follow-up.

So, this is a marker that is got very high sensitivity and specificity for testicular cancer. It reflects in a very timely way, and in a very active way, the disease activity. And the other advantage is that, compared to the standard conventional serum tumor markers that are in currently use, which is AFP and HCG, this test is positive in nearly all cases at diagnosis and across. It doesn’t matter what subtype of a germ cell tumor patients have, it’s positive too. So, that offers itself real clinical utility, which may improve patient management in the near future.

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