Aims Clear cell renal cell carcinoma (ccRCC) is the most common adult kidney cancer. It is an aggressive tumour with unpredictable outcome. The currently used clinical parameters are not always accurate for predicting disease behaviour. miR-10b is dysregulated in different malignancies including RCC.
Methods We assessed the clinical utility of miR-10b as a prognostic marker in 250 patients with primary ccRCC. We examined the correlation between miR-10b and clinicopathological parameters. We compared miR-10b expression among different RCC subtypes and normal kidney tissue.
Results We observed a stepwise decrease of miR-10b expression from normal kidney to primary ccRCC and a further decrease from primary to metastatic RCC. miR-10b expression was significantly lower in stages III/IV compared with stages I/II (p=0.038). Using a binary cut-off, miR-10b-positive patients had significantly longer disease-free survival (HR=0.47, CI 0.28 to 0.79, p=0.004). In the subgroup of patients with tumour size >4 cm, higher miR-10b expression was associated with significant longer disease-free and overall survival (p=0.001 and p=0.036, respectively). miR-10b was significantly downregulated in ccRCC compared with normal kidney (p<0.0001), and oncocytoma (p=0.031). It was also downregulated in chromophobe RCC. In addition, we identified a number of miR-10b-predicted targets and pathways that are involved in tumourigenesis.
Conclusions Our data point to miR-10b as a promising prognostic marker in ccRCC with potential therapeutic applications.
- RENAL CANCER
- TUMOUR MARKERS
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Handling editor Runjan Chetty
Contributors HWZK, LM, AK and AF were involved in obtaining fresh and formalin-fixed tissues and collection, interpretation and organisation of related clinicopathological parameters and survival information. HWZK was involved in RNA extraction and PCR analysis. HWZK and RN-M analysed data collected from The Cancer Genome Atlas database. AS was involved in the biostatistical analysis and explanation of its results. EL, SNK and YC were involved in data analysis and interpretation. HWZK and LY performed target prediction and pathway analyses. HWZK and ND contributed to the study design, data interpretation and drafting the manuscript. GMY is the senior author who was involved in all aspects of the project.
Funding Prostate Cancer Canada Movember Discovery Grants (D2013-39), Kidney Foundation of Canada (KFOC130030), Kidney Cancer Research Network of Canada, Canadian Institute of Health Research (MOP 119606).
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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