Tumour-specific profiling detects antibodies unique to stage I and II melanoma.
Australian-led research has made promising advancements in melanoma detection, which have the potential to significantly enhance diagnosis and prognosis by identifying the disease at its earliest stages.
The research was presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024, held in Amsterdam last month.
The method uses tumour-specific profiling to detect antibodies unique to stage I and II melanoma patients.
Melanoma produces immunogenic markers that trigger an immune response, resulting in the production of antibodies against cancer-testis antigens (CTAgs). These CTAgs lead to the production of specific antibodies that can act as early diagnostic and prognostic markers for melanoma, the researchers said.
In this study, a cancer array was used to analyse and compare blood samples from 199 patients with stage I and II melanoma and 38 healthy donors recruited through Lifeblood. Blood samples were collected at initial diagnosis and within 30 days of curative-intent surgery.
Specific IgG antibodies against three tumour antigens were identified as promising diagnostic biomarkers for early-stage melanomas, with area under the curve (AUC) values ranging from 0.857 to 0.981 in the discovery cohort and from 0.824 to 0.985 in the internal validation cohort.
Of the three identified markers, one showed an AUC value of 0.9805 in the discovery cohort, with 98% sensitivity and 76% specificity, and 0.9846 in the validation cohort, with 99% sensitivity and 82% specificity.
“These results indicate that 99% of melanoma patients in the validation cohort were positive for this marker, while 82% of healthy individuals were correctly identified as negative using the recommended threshold,” said Dr Cristina Vico-Alonso, lead researcher from the Victorian Melanoma Service at Melbourne’s The Alfred Hospital and Monash University.
“While 18% of healthy individuals were incorrectly identified as positive for this marker, combining it with the other two markers into a multiparameter signature does, however, help improve accuracy.”
Based on the validation data, only 1% of melanoma patients would have a negative test for this top marker, suggesting that a negative result is highly indicative of the absence of melanoma.
“It is important to note, though, that this cohort included healthy individuals with no prior or current cancers and excluded individuals at high risk of developing melanoma,” said Dr Vico-Alonso.
“Further testing in a real-world cohort is necessary to determine if these findings hold true when confounding factors, such as comorbidities, are considered.”
Dr Vico-Alonso said a significant advantage of this cancer array was its tumour-agnostic nature.
“CTAgs are expressed in many solid tumours, making the diagnostic signature identified here applicable beyond melanoma,” she said.
“However, the specific cognate antigen combination remains unique to melanoma compared to other solid tumours.”
She said work was currently underway using the cancer array to identify candidates for a pan-cancer diagnostic test, initially focusing on melanoma, lung, bowel and pancreatic cancers.
“In previous research, we identified a unique signature of antigens in advanced melanoma patients associated with more aggressive disease or metastases,” said Dr Vico-Alonso.
“Recently, we also identified another distinct antigen signature that differentiates between stage III melanoma patients who experienced recurrence and those who did not.”
The early detection of melanoma remains a challenge and this research represents a significant step forward, offering hope for more effective, non-invasive diagnostic tools. Critically, early detection can lead to earlier surgical and therapeutic interventions, reducing the number of patients presenting with advanced disease and improving outcomes.
“This method of early detection could be integrated into current melanoma screening practices to provide additional information, especially in uncertain cases, potentially avoiding unnecessary procedures,” said Dr Vico-Alonso.
