Melanoma represents Australia's national cancer and remains a significant public health concern due to its aggressive nature and rising incidence. Early detection is vital to improving survival outcomes. Liquid biopsies have emerged as promising non-invasive tools for cancer diagnosis, allowing the detection of circulating tumour-specific biomarkers such as nucleic acids, proteins, and antibodies. antibody-secreting B cells can produce antibodies against tumour-specific (TSAs) and -associated antigens (TAAs). Protein microarrays enable high-throughput antibody profiling against cognate TSAs and TAAs, providing insights into immune responses and potential diagnostic targets.
We hypothesised that circulating cancer-specific antibodies can detect melanoma early. Hence, we measured cancer-specific antibodies present at diagnosis in the plasma of 233 individuals accessed via the ACEMID cohort and the Victorian Cancer Biobank, comprising 37 with a prior history of cancer, 86 healthy controls, and cutaneous melanoma patients including 65 early-stage and 77 late-stage cases, using a custom protein microarray.
A univariate ROC analysis of the IgG and IgM antibody profiling data in the early-stage melanoma cohort identified antigens with significantly elevated antibody responses (AUC values ranging from 0.67 to 0.75 for IgG, and 0.74 to 0.86 for IgM). Further multivariate analysis using combiROC identified in a 6-marker IgG antibody signature (AUC = 0.827) and a 9-marker IgM antibody signature (AUC = 0.939) with strong diagnostic performance. We also performed a univariate ROC analysis in the late-stage melanoma cohort (AUC values ranging from 0.73 to 0.85 for IgG, and 0.72 to 0.86 for IgM). Here, a 6-marker IgG antibody signature (AUC = 0.86) and a 7-marker IgM antibody signature (AUC = 0.89) were identified. In addition, the same analytical pipeline was applied to a cohort with a prior history of cancer and successfully distinguished these individuals from healthy controls (AUC = 0.94 for IgG and 0.98 for IgM) and early-stage melanoma (AUC = 0.81 for IgG and 0.88 IgM). Together, these analyses reveal robust stage-specific antibody signatures with strong diagnostic potential.
In summary, this work underscores the value of antibody profiling as a minimally invasive biomarker discovery approach, offering new opportunities to improve the early detection of melanoma.