Editor: Dr. Emilie Clemmens
Motivation behind the research
Apparently unrelated diseases often appear together. For example, patients with post-traumatic stress disorder are more likely to have heart failure. The reasons for these associations are rarely resolved. The association between ALS and certain types of cancer is one such unresolved association.
Since genetic mutation are known to cause cancers, one might suspect associations between ALS and cancer might be related to common genetic mutations.
However, the majority of types of ALS are not associated with any genetic mutations, suggesting that something else is responsible for their clinical connection.
In this study, gene mutations were not considered. Instead of genetic mutations, we investigated the most expressed genes in the deltoid muscle of both ALS patients and healthy controls. Then, we identified 101 probes, each of which corresponds to a gene. Here, probes are a detector made out of a single molecule designed to quantitatively measure the amount of gene expression. These 101 probes can discriminate ALS patients from healthy controls with as high as 95% accuracy. On the other hand, genes assigned to these 101 probes are not only widely related with cancers but also used to predict survival probabilities of various cancers, including pancreatic and liver cancers. Thus, the identified genes likely bridge a missing link between ALS and cancers. Furthermore, these genes turned out to contribute to two important biological processes, one of which is related to protein transport within cells and another of which is related to protein translation. This suggests that malfunctions of these two identified biological processes might cause ALS and cancers. These findings might result in new therapies for both ALS and cancers, and may also help explain why some pharmaceuticals, such as the neuroprotective drug Riluzole, can be effective for both ALS and cancers.
This finding was based on the re-analysis of a limited number (19 humans) of publicly available data. Experimental validation is needed.
The statistical methods used for this study turned out to be very useful to relate genes expressed in diseases to diseases themselves. We are now planning to analyze more genes expressed in various diseases to identify correlations that can then be investigated experimentally to look for causal relationships between gene expression and the physiological manifestations of the disease.
Research Article: Genetic Association between Amyotrophic Lateral Sclerosis and Cancer, Genes (2017).