The National Institutes of Health this month awarded more than $1.6 million in grant funding to support four independent research projects examining the potential of microRNAs as biomarkers in three types of cancer, as well as in Alzheimer's disease.
The first grant went to Xifeng Wu, a researcher at the MD Anderson Cancer Center who is developing strategies for cancer risk prediction. As part of that work, and with the support of the NIH, she and her team aim to identify germline and circulating miRNAs that can be used to predict survival in late-stage non-small cell lung cancer (NSCLC) patients.
Having previously reported that single-nucleotide polymorphisms (SNPs) in miRNA-related genes could help predict clinical outcomes in colorectal adenocarcinoma patients, Wu now plans to look for similar correlations in NSCLC.
Taking advantage of MD Anderson's robust collection of specimens, the biomarker discovery and validation phases of their effort will each consist of 1,200 samples from platinum-treated patients to identify novel germline genetic loci in miRNA SNPs that correlate to patient survival.
A collection of 800 plasma samples from NSCLC patients will then be used to identify circulating miRNAs that may predict survival.
Results from the work are expected to help determine the disease-causing structural context, biological function, and molecular mechanism of the miRNA SNP and circulating miRNA biomarkers, Wu noted in her grant's abstract.
The project began on April 1 and runs for five years. It is worth $519,312 in its first year.
Washington University cancer biologist Xiaowei Wang was also awarded NIH funding this month to help with his investigations into miRNAs as biomarkers for cervical cancer.
In 2010, he and colleagues reported the discovery of a two-miRNA signature that could predict patient survival, based on the analysis of 102 cervical cancer samples.
With the NIH funding, Wang plans to "significantly expand" upon this preliminary work, analyzing all cervix-related miRNAs in a large number of cervical tumors, he wrote in his grant's abstract. "These miRNA biomarkers will then be combined to build a robust model for significantly improved prognosis of cervical cancer."
The grant began on April 1 and runs until March 31, 2016. It is worth $198,849 in the first year.
The third grant was awarded to Ohio State University's Ly James Lee, who will use the funding to test whether a novel extracellular RNA detection technology can be used with miRNA biomarkers for liver cancer.
Based on so-called tethered cationic lipoplex nanoparticles (TCLN), the approach involves molecular beacons, pre-loaded in liposome nanoparticles, that can capture circulating exosomes and detect encapsulated extracellular RNAs from patient blood or fluid samples, according to the grant's abstract.
Late last year, Lee and his colleagues published a paper demonstrating the technology in serum from lung cancer patients.
With the NIH funding, Lee plans to extend this work, specifically focusing on two miRNAs — miR-21 and miR-181b — that have shown biomarker potential both in a cancer mouse model and preliminary experimentation in liver cancer patient serum.
He specifically plans to use the nanoparticle approach to compare a panel of target RNAs as biomarkers in tumor tissue and blood samples from miR-122 knockout mice and transgenic mice with mutations in the Myc oncogene at different stages of disease.
Candidate mRNA/miRNA biomarkers arising from this study will then be evaluated in blood sampled from well-defined liver cancer patient groups to test the clinical potential of the TCLN assay.
Lee's grant began on April 1 and runs for two years. It is worth $193,200 this year.
The final grant was awarded to Eugenia Wang, founder of miRNA blood test developer Advanced Genomic Technology, to fund her company's efforts to develop a test that can use circulating miRNA expression patterns to test for mild cognitive impairment (MCI) and determine the risk of this condition converting into Alzheimer's disease (AD).
Preliminary studies suggest that a specific miRNA, miR-181b, is elevated in elderly patients who develop MCI, but not AD. Meanwhile, miR-34a and miR-34c increase only in MCI patients who go on to develop AD, but not in normal elderly individuals who develop MCI.
Wang will use the NIH funding to support research aimed at reproducing these findings using archived blood samples from 30 MCI patients, 30 normal elderly controls, and 30 AD patients. She also aims to identify other miRNAs from the miR-34, miR-181, miR-200, and let-7 families that may have potential as biomarkers.
This work will be followed by a study in additional cohorts of MCI and AD patients in order to validate candidate biomarkers and identify ones that may be used to differentiate AD from other dementias including Parkinson's disease.
The grant began on April 1 and runs until the end of 2015. It is worth $688,822 this year.