Besides, the team recognized a biological marker which may help determine the adolescent or young adult (AYA) patients who may develop more aggressive and cancerous fibrous tissues. In the future, this may help to make treatment decisions for such cases and thus able to help those patients who are expected to have better prognosis and require aggressive treatment, while mitigating the effects of overtreatment for those with early-stage cancers.
The study was led by researchers from The Institute of Cancer Research, London, and the results have been MAD valued published in Communication Medicine journal.
The study authors mention that this disparity in treatment outcomes can be attributed to a number of factors such as lack of services addressing age as a factor and minimal representation of AYAs in research studies. As a result, AYA patients do not benefit from effective therapies as the ones developed for patients aged 40 years and above.
Particularly the researchers focused on the histological evaluation of the sets of proteins expressed in patients of various ages, for which they developed a retrospective study rather than a prospective one.
The proteins that were subjected to study were present in the soft tissue sarcomas or desmoid tumors of 309 people. The patient cohort included nine types of sarcoma cases, namely angiosarcoma, clear cell sarcoma, and leiomyosarcoma among others. The team determined a total of 8148 proteins that were present in all samples analyzed while quantifying 3299 proteins. Out of those, 32 proteins were expressed in higher levels in AYA patients than in their older counterparts while 35 was expressed in older adults at a higher level than AYA patients.
The research demonstrated that older patients exhibited higher levels of cyclin proteins while the younger patients had more of structural proteins and proteins associated with mitochondrial energy-generating processes. These variations may impact the treatment outcomes of sarcomas which in turn, may affect the survival rates of the patients.
In the next part of the study, the research team aimed to assess whether there were any correlations between biological factors and the survival rates of participants. The analysis revealed that the elevated expression of particular subunits of the ribonucleoprotein complex corresponding to the biological splice- some was related to improved metastasis free survival (MFS). MFS is defined as the duration from the initiation of treatment to the occurrence of cancer spread. This splicing ‘signature’ could aid the treating physicians to optimally treat the AYA patients who are at a higher risk of cancer spread.
The first author of the study, Yuen Bun Tam, a Ph.D. student at the ICR in the Molecular and Systems Oncology Group, explained that “The existing treatments are not appropriate for use in the adolescent and young adult group of patients, which is very critical from the point of view of increasing survival rates in this particular age band.
As such, it is a grossly underserved area. In this study, we not only defined the biological characteristics of younger and older patients but also addressed a potential risk stratification signature which is age specific, that may be utilized clinically.
‘We hope that this will promote further research and clinical trials with adolescents and young adults as the focus in order to demonstrate the relevance of age in the development of more sophisticated interventions like targeting agents. This is ultimately going to have great benefits in improving survivorships as well managing late effects for this age group.’
The last author Dr. Paul Huang, who heads the Molecular and Systems Oncology Group at the ICR, explained, “We had anticipated that there would be differences in biology of the two tumor types that made up the patient cohorts; however, we did not expect most of them to be associated with the mechanisms and histological subtypes of sarcoma.”
Reference
Yuen Bun Tam et al, Proteomic features of soft tissue tumours in adolescents and young adults, Communications Medicine (2024).
