Gastric cancer (GC) is a worldwide malignant neoplasm of undoubted lethality and is endemic in East Asia, Eastern Europe, and South American countries. The main problem with GC is that it is often detected at an advanced stage, and the survival rate is less than 10%. In comparison, the survival rate can be as high as 90% for early-detected GC cases. As a result, the development of new detection methods has become a necessity for identifying early-stage GC cases.
The so-called jumping genes, transposable elements (TEs), are rarely studied due to their computational challenges. In the last few years, a considerable number of studies have been carried out using TEs to get an idea of these elements in various types of cancers. Despite this, the impact on GC has not been studied previously.
In stark contrast, nearly 50% of the human genome corresponds to transposable elements, which are highly repetitive elements due to their ‘jumping’ nature: TES can replicate and move around the genome. They were originally called ‘junk deoxyribonucleic acid (DNA)‘ since these elements seemed to be parasitic and self-centered, intended to create more genetics. Barbara McClintock revealed the importance of TEs in controlling gene expression and was awarded the Nobel Prize in 1983.
More recently, it has become well-known that TEs play a role in gene regulation in both healthy and disease contexts, as reported by the research team. Barbara McClintock said, “The development of computational tools for their study has been made possible through my and other lab contributions.”
GC transposable elements
The team validated and characterized that TE activation is a hallmark of GC. They concluded this by assessing TE activation in spatially resolved ribonucleic acid (RNA) sequencing data. While computational modeling of cell evolution, ‘trajectory inference,’ is an area of key development, it has not been utilized broadly for cancer study. The researcher combined the approach with their knowledge of TEs to characterize cell evolution and discovered that 111 of these jumping genes are activated in the malignant cell lineages.
With spatially resolved data they could see the expressions in the tissue as it is. Accordingly, they found out that TEs are activated in both tumor regions and their environment. In some instances, they even discovered that TEs track the transition from normal to tumor regions, corresponding to the results obtained from the first part of their study.
Finally, a network of TE-mediated gene regulation was modeled, demonstrating that ~ 2,000 genes could be regulated by TEs, with ~ 500 of these already associated with cancer. Also, activated TEs may influence gene regulation and potentially contribute to the progression of GC. The detection of these ‘jumping genes’ would then be regarded as novel biomarkers for early detection of GC. This research will next attempt to experimentally validate these findings and if these elements are consistently detected in the early stages, we may have a novel means of fighting and treating GC.
Reference: Valdebenito-Maturana B. The spatial and cellular portrait of transposable element expression during gastric cancer. Sci Rep. 2024;14:22727. doi:10.1038/s41598-024-73744-7
