Mesothelioma research often investigates potential biomarkers and agents that could offer new pathways for diagnosis and treatment. In recent years, researchers have found a variety of new biomarkers that can differentiate mesothelioma from other cancers, like fibulin-3 and HMGB1. Currently, the only way to definitively diagnose mesothelioma is through a biopsy. In many cases, a tissue biopsy is needed, as the cytological testing of a fluid sample may not always be as accurate and clear as needed for a proper diagnosis.
A new study is looking at the potential of different microRNAs in pleural effusions (fluid buildup in the pleural cavity) as a unique identifier of malignant pleural mesothelioma. In this new clinical trial, researchers sought to identify new ways to diagnose mesothelioma by testing for increased or decreased amounts of particular microRNAs in fluid samples. The study found three potential microRNA expressions that could identify pleural mesothelioma.
Identifying MicroRNA Biomarkers in Mesothelioma
Pleural effusions are a common symptom of mesothelioma, with research indicating about 80 – 95% of pleural mesothelioma patients have a pleural effusion when diagnosed. Though pleural effusions typically indicate a more advanced stage of mesothelioma, researchers note that the fluid offers many potential biomarkers that can lead to a proper diagnosis, including microRNAs.
MicroRNAs regulate gene expression and influence a variety of cellular functions, like cell development, differentiation and growth. The researchers of this latest study note microRNAs are ideal targets as biomarkers because they have stability in the body. In previous studies, microRNAs from tissue, blood and serum have been evaluated for diagnostic purposes, but showed mixed results and require further study. There has been limited research around the potential of microRNAs in pleural effusion samples so far.
In order to determine if pleural effusions in mesothelioma patients contained identifying microRNAs, the researchers obtained fluid samples from patients with adenocarcinoma and benign effusions for comparison. The 26 pleural mesothelioma fluid samples consisted of mostly epithelioid cell type, but also referenced two sarcomatoid samples and one biphasic sample. The patients were mostly male and ranged from 60 – 80 years old.
The researchers analyzed 758 microRNAs to determine which ones could work as novel targets for diagnosis. They first identified which ones were significantly upregulated or downregulated compared to the control group. Upregulation refers to an increase in the quantity of a cellular component like microRNA, while downregulation refers to the decrease of a particular microRNA. At this point, researchers identified 11 potential targets showing upregulation or downregulation.
The 11 targets were then narrowed down based on which microRNAs were uniquely expressed within the mesothelioma samples and could be potential identifiers. With this analysis, researchers identified a combination of three microRNAs that could differentiate mesothelioma from other diagnoses:
The combination of the three microRNAs showed an approximate 95% accuracy in differentiating mesothelioma from other malignancies. The researchers further noted the combination offered a 92 – 98% sensitivity, or the probability that the test will accurately diagnose mesothelioma.
The Potential of MicroRNAs for Diagnosis
Mesothelioma researchers and doctors constantly seek improved diagnostic methods for the rare cancer. Because of its long latency period and nonspecific symptoms, mesothelioma is difficult to diagnose early. While the presence of pleural effusion can assist in diagnosis, researchers note it can still be difficult to differentiate from other malignancies. Additionally, it can be costly and time-consuming to stain a sample for particular antibodies like fibulin-3.
MicroRNAs may offer a solution for diagnosis and treatment targets in mesothelioma and other types of cancer. In recent years, several mesothelioma studies have examined the potential of these molecules in diagnosing mesothelioma from tissue biopsies, determining prognosis and treating the disease. However, more research is needed to understand the efficacy of microRNAs as a diagnostic tool and how they could be targeted for treatment.
With further study in a larger patient group, researchers hope this combination of miR-143, miR-210 and miR-200c can offer a more timely, cost-effective and accurate solution for mesothelioma diagnosis.