A recent finding from a team of researchers from Italy has good news for women at risk of developing epithelial ovarian cancer. Scientists have developed a molecular predictor that measures miRNA (microRNA) levels as risk determinants for epithelial ovarian cancer. The study was also published by journal The Lancet.
With a recurrence rate of as high as 80%, only about 45% ovarian cancer survivors live up to a five-year long post-disease span. The whopping risk rate of disease relapse or progression for women who have suffered epithelial ovarian cancer, had led the oncology experts to delve into the working mechanisms of disease progression and devise scientific techniques to speed up diagnosis and treatment. miRNA profiling seems to be one such screening tool.
Highly conserved non-coding endogenous RNA molecules known as miRNA have emerged as a promising candidate to solve many medical riddles. Discovered in 1993, the role of miRNA was vaguely defined earlier. However, miRNA today is at the forefront for cancer diagnostic tests.
In this cohort study, 179 miRNA expression profiles were collected and analyzed for diagnosis from Multicenter Italian Trial in Ovarian Cancer. While further two cohorts of 263 and 452 samples were collected to validate the findings of the first cohort, these samples were collected from the Center Genome Atlas epithelial ovarian cancer series and other cancer centers.
The miRNAs were analyzed to predict the risk of cancer progression in the patients. During this demonstration, 35 miRNA were identified to be linked to the occurrence of epithelial cancer. Out of the 179 samples, 89 patients were at a high risk of cancer progression with a median progress-free period of 18 months. On the other hand, 90 patients were at a low risk, having a median progress-free period of 38 months.
The results indicated the role of miRNA profiling as a significant predictor for cancer progression in epithelial ovarian cancer.
MicroRNA has a major role to play in human body as it contributes towards gene expression regulation by targeting mRNA for degradation which eventually results in translational repression. Adding onto new dimension of human biology, the effects of miRNA at a molecular level are complex. With the advent of next generation sequencing techniques, the role of miRNA is better defined with every coming day. Comprising of only 20-26 nucleotides, the role of miRNA is present in numerous biochemical pathways. Under normal working conditions, the miRNA may help increase the precision of gene expression and they may act as a biological switch between many differential pathways. Interestingly, 60% of all messenger RNA regulatory processes have their roots in miRNA mediated regulation which in turn affects the post-translational protein products.
Thereby, miRNA has a significant role in cell proliferation, differentiation, defining cellular identity and programmed cell death. The miRNA binds to the untranslated region of mRNA which is undergoing translation to produce a protein. This miRNA-mRNA interaction leads to either reduced translation or deadenylation of mRNA that terminates translation. These translation regulation processes are crucial for the healthy functioning of body. Otherwise, miRNA dysregulation could lead to fetal diseases like cancers. Identified in 2013, at a contributing factor in cancer, miRNA dysregulation in cancer is accompanied by distorted negative feedback leading to uncontrollable cellular proliferation.
The profiling of tumor related miRNAs has an immense potential to define cancers by subtypes, survival rates and most effective treatments.
The study has a potential to classify cases of epithelial ovarian cancer based on the risks of relapse or progress by monitoring miRNA levels at a clinical level. However, further investigations are warranted to refine this molecular diagnosis. Despite the discovery of over 2,500 miRNAs in humans, the use of miRNA has a molecular diagnosis agent has many limitations attached to it. As mentioned above, the regulatory role of miRNA is complex in nature, controlling a cascade of events simultaneously. Targeting multiple target mRNA at a time to pinpoint one target that increases the likelihood of tumor, is hard.
Furthermore, all the miRNA molecules do not govern by a role of thumb in triggering oncogenes. If a target miRNA is increasing the risk of epithelial ovarian cancer in one individual, it is not necessarily causing the same effects in another patient suffering from same cancer type. An individual’s genetic susceptibility to the effect of a certain miRNA is of a crucial value. Adding more to the complexity, the role of miRNAs remains peculiar in many cases. Sometimes, miRNA upregulates the effects of oncogenes while at other times miRNA downregulates the function of tumor suppressor genes.
However, in near future it is hoped that oncology experts will devise a mechanism to overcome these limitations and make use of miRNA profiling as a regular clinical practice to predict the risk of cancer progression as a non-invasive liquid biopsy tool.
As opposed to undergoing the conventional, time-consuming, costly and painful procedures of chemotherapy, radiation therapy and surgeries, the molecular predictive tool can revolutionize the way ovarian cancer is treated. With better understanding of molecular determinants, drug therapy will also be mainstreamed as personalized medicine for cancer patients.