Retroperitoneal liposarcoma tumors can be categorized into two distinct molecular subtypes. Those with strong expression of a gene known as LEP and minimal expression of a gene called PPTG1 are less aggressive (top), while high PPTG1 expression and low LEP expression indicates tumors will be more aggressive (bottom). Image credit: Xiao et al. (CC BY 4.0).
Retroperitoneal liposarcoma (or RPLS for short) is a rare type of cancer that forms a tumor deep in the abdomen. Although it can be treated through surgery, results vary widely, and the cancer often returns. Determining which RPLS tumours are likely to respond well to treatment, and which are more aggressive, can be challenging. This is partly because many of the tumors appear similar under a microscope, making it difficult to identify those that might require more intense treatment.
For some types of cancer, researchers have started to overcome this problem by identifying molecular markers – specific genes, proteins and other molecules – that are unique to tumor cells. This allows for a better understanding of tumor behavior and helps pinpoint which treatments are most likely to be successful. However, the relevant molecular markers for RPLS remain unknown, preventing this precision medicine approach from being applied to this type of cancer.
To help close this gap, Xiao et al. studied the genetic activity of tumors from 88 RPLS patients to look for activity associated with more aggressive tumors. Analysis revealed two distinct groups of tumors. One group showed high activity of a gene known as LEP, which is involved in metabolism. Tumors with high LEP activity were less aggressive, with patients surviving longer and requiring fewer surgeries. The other tumor group showed high activity of a gene known as PTTG1, which plays a role in cell division and DNA repair. When overactive, these processes can make tumors grow and spread more quickly. In this group, tumors were more likely to return after surgery. Based on these findings, Xiao et al. developed a simple test using the two genes to classify tumors. When tested in a larger group of 241 patients, this method successfully sorted tumors into the two groups with more than 99% accuracy.
The findings of Xiao et al. suggest that the activity of LEP and PTTG1 could potentially be used as a molecular marker for identifying RPLS patients that might benefit from more intensive treatments. However, further research is required to confirm how reliable these markers are before they can be used to diagnose patients in the clinic.
