Esophageal cancers are one of the more common cancers around the world, with an unfortunately poor prognosis. The five-year survival rate is around 20% when caught in its late stages. However, when it is caught in its early stages, preventative treatment is incredibly effective. The available tests are somewhat invasive however, and many early-stage esophageal cancers slip by. The search for biomarkers to come up with better diagnostic tools to overcome these shortcomings has led a group from Japan to miRNAs, specifically to a newly identified group called isomiRNAs.
MiRNAs are small snippets of RNA that can regulate the expression of proteins by binding target mRNAs. Immature variants of these miRNAs, called isomiRNAs, have recently been identified. These variants have unique mRNA targets. Both kinds of miRNAs are present in blood serum, are incredibly stable, and have been shown to have a change in levels upon cancer formation. Taken together, these characteristics make miRNAs an excellent target for possible biomarkers. Other groups have already identified potential miRNA targets. IsomiRNAs, however, are still relatively unstudied.
The group began by retrieving blood serum samples of esophageal cancer patients from a hospital store, as well as healthy blood serum to use for controls. After purifying the miRNA from the serum, statistical analysis was used to identify miRNAs that had higher levels in cancer patients versus the control group. From 5451 identified miRNAs in the blood serum, 24 hits were found to have statistically significant changes in levels. From these 24 hits, three were further identified as lead targets for the study.
These three consisted of one miRNA and two isomiRNAs. The miRNA is a lead in a few other papers, showing it might be useful in the diagnosis of a variety of cancers. The two isomiRNAs are novel, however, and present yet more possibilities for possible biomarkers. Examining these miRNAs in the serum samples, they observed an increase in levels of all three in the esophageal cancer serums versus healthy serum. As all initial samples were pre-treatment, they measured the same miRNAs in post-treatment and found that they were all down to normal, healthy levels. Four of the patients, unfortunately, went into recurrence, and samples from these patients showed an increase in the levels of lead miRNAs. These surprising observations make all three miRNAs great candidates for further studies.
The use of miRNAs as biomarkers against cancer is quickly becoming a lead diagnostic possibility. Their strong stability and relative ease in obtaining from patients make them great candidates for quick and effective diagnosing tools. This group investigated the use of miRNAs and isomiRNAs in diagnosing esophageal cancer and surprisingly found them effective not only in initial testing but even in testing for any recurrence post-treatment. This work is still early in the discovery process, however, but with any luck will result in new tools in the fight against cancer.