Image: An example of a TaqMan Low Density Array card; each well contains a specific miRNA forward primer, a specific miRNA TaqMan probe, and a reverse \"tail\" primer (Photo courtesy of Dana-Farber Cancer Institute).
Kidney cancer is usually caught because of the symptoms a patient develops, but it is also possible for kidney cancer to be asymptomatic, with tumors growing quite large before causing pain or other noticeable problems.
The mechanisms involved in renal cell carcinoma (RCC) development and progression remain unclear, and new biomarkers are needed in routine practice to improve the diagnostic and/or prognostic accuracy. A blood test for kidney cancer, which is under development, could improve screening for this disease and help ensure that asymptomatic patients are diagnosed while their cancer is still treatable.
A team of scientists at the Jinling Hospital (Nanjing, China) measured the concentrations of 754 different microRNAs (miRNA) in blood samples from 33 patients with the most common type of kidney cancer (renal cell carcinoma) and 33 healthy individuals. An initial microarray survey of 754 miRNAs was firstly performed using the TaqMan Low Density Array followed by a hydrolysis probe-based quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation from serum samples to identify significantly dysregulated miRNAs in RCC. The expression levels of miR-651 and miR-708 in 17 paired tumor tissues were also examined. Furthermore, in vitro tests including CCK8 proliferation, transwell and wound healing assays were conducted to explore the potential functions of miR-651 and miR-708 in RCC. Luciferase reporter assays combined with Western blotting were employed to validate the target genes.
The team found that the serum levels of four miRNAs were verified to be significantly increased, whereas the levels of four miRNAs were markedly decreased in RCC patients compared with the non-cancer controls. Of these eight microRNAs, statistical analysis revealed that the two known as miR-651 and miR-708, which decreased in the kidney cancer patients, exhibited the largest areas under the curve (0.888 and 0.832, respectively). This means that a test for these microRNAs could diagnose renal cell carcinoma with relatively high accuracy. They also investigated the functions of miR-651 and miR-708 and found evidence suggesting they act as tumor suppressors. A therapeutic that increases levels of miR-651 and miR-708 could therefore potentially serve as a new treatment for renal cell carcinoma.
Chunni Zhang, PhD, the lead author of the study, said, “The mechanisms involved in renal cell carcinoma development and progression are unclear, and there is no standard serological biomarker to facilitate diagnosis in patients with this disease. Both miR-651 and miR-708 may potentially serve as novel biomarkers for renal cell carcinoma and may act as tumor suppressors. Our findings indicate that targeting miR-651 and miR-708 by a genetic approach may provide a novel strategy for the treatment of renal cell carcinoma.” The study was presented at the 69th AACC Annual Scientific Meeting & Clinical Lab Expo, held July 30 to August 3, in San Diego, CA, USA.