Biological discoveries pave the way for better outcomes for young adults with sarcoma

A recent study has answered the question of why survival gains for young people with soft tissue cancers lag behind those of their pediatric and older adult counterparts. By analyzing the protein profiles of different types of soft tissue tumors, called sarcomas, the researchers showed that there are distinct biological differences between these age groups.

Additionally, the team identified a potential biomarker that could help predict which adolescent and young adult (AYA) patients are likely to have aggressive forms of sarcoma that will spread to other areas of the body.

In the future, this could help guide treatment decisions for people of this age, improving outcomes for patients who are expected to need more intensive treatment and sparing those with less aggressive cancer the side effects of overtreatment.

Researchers from the Institute of Cancer Research in London conducted the study, which was published in the journal Communication medicine.

Age affects outlook for people with soft tissue tumors

Soft tissue tumors develop in the connective and supporting tissues of the body, such as muscle and fat. They are relatively rare, but can affect people of any age. Those that are malignant (cancerous) are called sarcomas.

Although the incidence of sarcoma is higher in the AYA age group than in older adults (accounting for 8% of cancer diagnoses versus only 1%), improvements in survival rates in the AYA age group, defined as those aged 16 to 39 years at diagnosis, have not kept pace with those in patients in other age groups.

The study authors point out that there are multiple reasons for this disparity, including a lack of age-specific services and underrepresentation of people in the AYA age group in clinical trials. These factors mean that current treatments are optimized for people aged 40 and older and are not always effective for AYA patients.

Convinced that biological differences between age groups must play a role in these inconsistent results, the researchers set out to retrospectively analyze the characteristics of the sets of proteins expressed in patients of different ages.

They used data from 309 people with soft tissue sarcomas or benign soft tissue tumors called desmoid tumors. Nine types of sarcomas were represented in the cohort, including angiosarcoma, clear cell sarcoma, and leiomyosarcoma.

Identifying a new way to predict the spread of cancer

The researchers identified a total of 8,148 proteins across all patient samples and quantified 3,299 of them. They found that 32 of these proteins were more abundant in AYA patients than in older adults, while 35 were more abundant in older adults. After the researchers adjusted the results for other variables, including tumor size, anatomic site, and sarcoma subtype, five of these proteins remained significant.

Overall, older patients had higher levels of a protein involved in cell cycle regulation, while the more abundant proteins in AYA patients play a role in the structural support and function of mitochondria, which generate energy for cells.

These differences could affect how sarcomas respond to treatment, which in turn will influence people’s likelihood of survival.

In the next part of the study, the team wanted to determine whether there was a correlation between biological factors and the participants’ survival rates. The analysis showed that high expression of specific subunits of the cellular machinery responsible for splicing – an important step in the protein synthesis process – was associated with better metastasis-free survival (MFS). MFS is the time between the start of treatment and the start of the cancer’s spread.

This splicing “signature” could potentially be used by clinicians to identify AYA patients most likely to need intensive treatment to prevent their cancer from spreading.

“This could lead to substantial improvements in survival.”

Yuen Bun Tam, first author and PhD student in the ICR Molecular and Systems Oncology Group, said: “The lack of tailored therapies for adolescent and young adult patients is a major barrier to improving survival rates in this age group, representing a significant unmet need. In this study, we not only characterised the biological differences between young and older adult patients, but also identified an age-specific signature that can be used as a risk stratification tool in the clinical setting.”

“By demonstrating the importance of age-specific studies in discovering more tailored strategies, such as targeted agents, we hope our results will encourage future studies and clinical trials to include more adolescents and young adults. In the long term, this could lead to substantial improvements in survival and management of late effects for this age group.”

Lead author Dr Paul Huang, Head of the Molecular and Systems Oncology Group at the ICR, said: “Although we predicted that there would be inherent biological differences between the tumours of the two groups of patients, we were surprised to find that many of these findings were independent of other clinical factors that differed between the two age groups, including sarcoma type.

“We plan to continue our work to validate our results in larger cohorts and to measure our splicing signature, in the hope of being able to use it as a clinical test. We will also work to better understand the link between this splicing signature and the ability of the tumor to spread.

“This knowledge could help identify new therapeutic options for managing soft tissue tumors in adolescents and young adults.”