By Doug Macron
Rosetta Genomics this week announced the availability of the second-generation version of miRview Mets, a diagnostic designed to use microRNA signatures to determine the sources of tumors of unknown primary origin.
According to the company, miRview Mets 2 can identify 42 tumor types, up from 25 types identifiable with the first-generation version of the test.
"The new assay offers identification of sarcomas, lymphomas, and other non-epithelial malignancies, as well as more histologic subtypes," Rosetta said. "Furthermore, the test features improved classifiers which incorporate clinical, biological, and molecular knowledge."
After recently regaining the rights to the miRview Mets line, along with its two other commercialized miRNA diagnostics, from former marketing partner Prometheus Laboratories (GSN 12/2/2010), Rosetta said the test is directly available from its Philadelphia-based laboratory.
Having advanced three miRview tests to the market, Rosetta currently leads the miRNA-based diagnostic field, but it is not alone in seeing potential from the small, non-coding RNAs. More than a dozen research groups in the US and overseas are currently examining miRNAs as biomarkers in a clinical setting.
And although most of the efforts aim to link miRNA expression patterns with malignancies, other disorders under examination include HCV infection, asthma, sepsis, and inflammatory bowel disease, according to a review of clinicaltrials.gov, an online clearinghouse for clinical trial information established by the National Institutes of Health.
In the US, the City of Hope Medical Center is currently recruiting breast cancer patients receiving neoadjuvant or adjuvant treatment in an effort to examine miRNAs as prognostic indicators in the disease and as predictors of response to particular therapeutics.
"Dysregulation of specific miRNAs may be associated with either gaining oncogenic or losing tumor suppressing functions … [and has] been implicated in breast cancer tumorigenic and non-tumorigenic development," COH notes in an overview of the study. "Therefore, miRNA profiling of treatment-naive and treatment-exposed breast tumors, and sequential samples of blood/serum, will allow for identification of miRNA markers of prognosis and as indicators and potential targets for personalized therapies."
Meanwhile, Memorial Sloan-Kettering Cancer Center is conducting a study looking at the role of miRNAs in the biology of the abnormal breast tissue lesion called lobular carcinoma in situ, which is not cancerous but has been linked to an increased risk of cancer.
The institute said it will look for the lesion in tissue removed from patients with breast cancer or from those who are at high risk for the disease. If it is found, it will use "microarray-based gene expression profiling to determine whether a unique mRNA and microRNA gene expression profile distinguishes [the lesion] from normal breast epithelium and from invasive carcinoma," MSKCC said.
The National Cancer Institute is preparing to launch a study this month that will obtain RNA from tissue samples of infants with acute myeloid leukemia in order to identify biomarkers for the disease. Specifically, the NCI said it will sequence miRNAs from 20 samples and compare them to infant acute lymphoblastic leukemia samples to help identify lineage- and translocation-specific miRNAs.
The NCI also plans to begin looking at tumor tissue from patients with stage I or stage III endometrial cancer in order to find miRNAs associated with lymph node metastasis, and to launch a study that will analyze specimens from neuroblastoma patients up to age 18 for miRNA patterns that have "prognostic significance … as accumulating evidence indicates that alterations in miRNA expression play a critical role in tumorigenesis and can be used in prognostic evaluation," according to clinicaltrials.gov.
Beyond cancer, Ohio State University is looking at miRNA expression in patients with pulmonary arterial hypertension in order to "see if blood samples can be tested to determine who might develop PAH, how well drugs will work to treat PAH, and to learn more about the development" of the condition, according to OSU.
The university is also investigating whether patterns of serum miRNAs can help determine the causes of increased asthma symptoms experienced by a "small number" of women with the disease during their premenstrual or menstrual period.
At the Rogosin Institute in New York City, researchers have launched a study to assess whether miRNAs obtained from urine can be used as biomarkers for characterizing patients with autosomal dominant polycystic kidney disease compared with patients with other causes of chronic kidney disease, according to clinicaltrials.gov.
"Biochemical and computational analysis of small RNAs from these samples will provide urine miRNA profiles and key variability statistics that will be used to design follow-up projects involving patients with kidney disease," the institute states.
Outside of the US, Sun Yet-Sen University in China is currently seeking patients with renal cell carcinoma to participate in a study examining the role of miRNAs in their disease.
"In this study, renal cell carcinoma-related miRNA and the target genes of related miRNA will be examined, and the relationship between [the miRNAs and the cancer's] pathological types, tumor-nodes-metastasis stages, and prognosis will be analyzed," the university states.
Also in China, at PLA General Hospital, investigators are collecting and analyzing miRNAs obtained from the serum of patients with sepsis to evaluate their association with prognosis and examine their potential as targets for the condition.
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In Canada, at the University of Alberta Hospital, researchers are collecting miRNAs from solid organ transplant patients with cytomegalovirus in order to follow up on the previous finding that a specific miRNA, miR-UL-112-1, down-regulates the expression of CMV genes involved in its own replication process as a means to maintain cell viability and persistent infection.
"The purpose of this study is to assess how the virus interacts with the patient's immune system so that in the future it may be possible to develop better ways to prevent and treat the virus infection," the university writes.
The Tel-Aviv Sourasky Medical Center in Israel is currently examining whether miRNAs control the inflammatory response in inflammatory bowel diseases through regulation of expression of the mRNA of the enzyme acetylcholine esterase.
"There is a reciprocal relationship between the central nervous system and the immune system," the institution writes. "Stimulation of the vagus nerve results in secretion of acetylcholine, which decreases secretion of pro-inflammatory cytokines. Acetylcholine esterase is an enzyme that neutralizes Ach and, thus, [is involved] in regulation of Ach levels, and in the cholinergic tone and inflammatory state."
At the National Taiwan University Hospital, researchers are conducting a number of studies to examine miRNAs and disease, including one aiming to establish improved risk classifications and minimal residual disease detection for risk-directed therapy for childhood acute lymphoblastic leukemia.
As part of that effort, the hospital will collect miRNA expression profiles from adolescent ALL patients given the increasing evidence that the small RNAs can be used to classify cancers.
The National Taiwan University Hospital is also enrolling HCV patients in a study that will examine miR-122, which has been shown to play a role in the virus' replication, as a potential blood-based biomarker to monitor the disease.
"Liver biopsy is … considered an invasive procedure, which prevents its widespread use in routine clinical practice," the hospital writes. "Considering the abundant blood flow through the liver, we speculated that miR-122 can be detected in the sera, and can be used for screening and monitoring" of patients to determine treatment responses to peginterferon and ribavirin combination therapy.
The hospital is also recruiting patients with liver cancer to examine miRNA expression patterns to "develop a predictive signature for postsurgical survival" in light of studies showing that specific microRNAs are aberrantly expressed in malignant hepatocellular carcinoma tissues compared to normal tissue, it states on clinicaltrials.gov.
And in Germany, the Wuerzburg University Hospital is enrolling patients with high-risk prostate cancer to collect miRNA samples in order to determine whether specific expression profiles of the ncRNAs are related to disease outcome.
In France, at the Centre Hospitalier Universitaire de Nice, investigators are analyzing the "differential expression of the miR transcriptome in the distinctive stages of the development of cutaneous squamous cell carcinoma," according to clinicaltrials.gov.
A total of 20 patients with the disease are being recruited to provide biopsies of normal, pre-tumoral, and tumor tissues from which miRNAs will be collected and analyzed for their potential role in the skin cancer.
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