MicroRNAs hold promise as markers for bladder cancer prognosis

By Sally Robertson, B.Sc.Feb 18 2013

Researchers have found that microRNAs can be useful prognostic biomarkers for individuals with urothelial carcinoma (UC).

In a follow-up analysis of 137 individuals with UC, progression of non-muscle-invasive (NMI) disease was associated with significantly altered levels of microRNAs, report Ofer Nativ (Bnai Zion Medical Center, Haifa, Israel) and colleagues.

In particular, high expression levels of the microRNA miR-29c* were associated with a good prognosis, they say.

As reported in BJU International, 29 of the tumor samples analyzed by the team were classified as muscle-invasive cancers and 108 as NMI. Of the 108 patients with NMI cancer, 79 did not progress to T2 or higher stages (no progression [NP] group) during a median follow-up period of 53 months, while 29 progressed to muscle-invasive cancer (invasive progression [IP] group) over a median of 14 months.

The researchers microdissected 19 of the samples and compared microRNAs that were present in tumor-only tissue with those contained in the full sample. For five samples, they also microdissected muscle and lamina propria and compared all of the sample components. Twenty-six microRNAs that were predominantly expressed in non-tumor tissue but were also expressed in the full sample were identified; these were excluded from the analysis so that only tumor-specific microRNAs were studied.

On comparing tumors from the IP and NP groups, the team found four tumor-specific microRNAs that showed significant, more than two-fold differences (in either direction) between NP and IP samples, namely, miR-29c*, miR-182, miR-130a, and miR-3. The greatest level of significance was seen for miR-29c*, with a 2.1-fold higher expression in NP versus IP samples.

Furthermore, the lower expression levels of miR-29c* in patients who later progressed were similar to those observed in patients who already had a muscle-invasive cancer at baseline.

Stratification of the NMI sample cancers by high, intermediate, or low expression of miR-29c* showed that, among those in the highest tertile, only two (5.6%) individuals had cancer progression and only one progressed within 5 years (2.6%). By contrast, those in the lowest tertile had a median progression-free survival of only 35 months, with a 50% progression rate.

"Thus, the expression of miR-29c* holds significant value in risk stratifying patients with NMI bladder cancer," say Nativ et al.

"The usefulness of microRNAs for determining prognosis for patients with UC should be assessed in larger prospective studies, as they could have a substantial impact on the choice of treatment and follow-up of the individual patient," they conclude.

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