European researchers have identified two microRNAs, or small non-coding RNA molecules, that can be used to predict outcomes of malignant pleural mesothelioma, in an international study that aimed to clear up the confusion caused by earlier contradictory findings.
The study, “Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism,” appeared in the journal Scientific Reports. It pinpointed a range of other microRNAs important in mesothelioma development, giving researchers a better understanding of the factors driving disease development and progression.
Researchers at Italy’s University of Pisa and England’s University of Salford analyzed microRNA profiles from 96 patients with pleural mesothelioma and 10 normal pleura samples. The first screening came up with no less than 63 microRNAs present in abnormal amounts in cancer tissue. Most were produced at lower quantities than in normal tissue, but eight were higher.
To verify their findings, researchers selected the five microRNAs that deviated the most from healthy tissue. All were found in lower levels in mesothelioma, compared to control samples.
Using another group of 16 patient-derived and 17 control tissues, the team found that three microRNAs were lower also in this group of mesothelioma patients. But their initial list also contained microRNAs that other studies had suggested play a role in mesothelioma, confirming their likely role in the disease.
MicroRNAs are factors that act to control gene activity. Each microRNA controls several genes, so knowledge of how they are linked to disease must be coupled with information about which genes they control to gain meaningful insights into disease mechanisms.
Researchers used computer software and databases of biologic interactions to track down the genes and molecular pathways most likely influenced by the identified microRNAs. They found pathways known to promote cancer growth, as well as common cell signaling pathways. Finally, they correlated the levels of the microRNAs to survival data in patients, and found that a signature of two microRNAs could be used to predict survival — even when other factors such as age at diagnosis and mesothelioma subtype were considered.
The two, called Let-7c-5p and miR-151a-5p, have been related to poor outcomes in other cancer types, and are linked to cell metabolism functions. In addition to the two microRNAs, better survival was dependent on treatment, including chemotherapy, radiotherapy and surgery.
Patients identified as high-risk using the two-microRNA signature could benefit from more targeted, aggressive treatments targeting cell metabolism, researchers said.