Abstract 5346
Background
Melanoma is the most aggressive of common skin cancers. We aimed to create a polygenic risk score (PRS) and evaluate its capability to predict melanoma prognosis better than staging.
Methods
The cohort included 1126 melanoma patients (567 males, 559 females); 57%, 24% and 19% patients stage I, II and III at diagnosis, respectively. The mean age at diagnosis was 54 yo (range 12-97). We genotyped 252 candidate SNPs by OpenArray. After quality control, we selected SNP associated with disease-free survival (DFS) and melanoma-specific survival (MSS) (log Rank P < 0.05), in the whole cohort and independently by sex. We performed cross-validation using 2/3 for training and 1/3 for validation. If the model was consistent in the three comparisons (concordance rate > 0.75), we created a PRS based on the weight of each SNP in MSS or DFS modulation. We compared the score including PRS and clinical data (age, sex, staging), with the clinical score alone or the staging score alone. ROC curves were calculated for each score to assess the capability to predict DFS and MSS.
Results
We identified 29 SNPs associated with DFS survival in the whole cohort. The score with PRS had a higher prediction capability (AUC 0.844), compared to clinical score (AUC 0.770) or staging alone (AUC 0.741). Male-specific analyses revealed 8 male-specific SNPs. The male-PRS improved also the prediction capability (AUC 0.831), compared to clinical (AUC 0.760) or staging alone score (AUC 0.735). Female-specific analyses revealed 21 female-specific SNPs. The female-PRS improved also the prediction capability (AUC 0.868), compared to clinical (AUC 0.767) or staging alone score (AUC 0.742). Using an optimal PRS + clinical score cut-off, we improved the classification of patients into low and high-risk groups within each stage and comparison (Table). Similar results were obtained regarding MSS.Table:
1366P 5-year DFS rate (%)
Sex | Stage | ALL | Low-risk group | High-risk group |
---|---|---|---|---|
ALL | I | 92.5 | 94.9 | 62.7 |
II | 69.7 | 87.7 | 50.6 | |
III | 59.3 | 90.2 | 50.3 | |
MALE | I | 91.4 | 92.0 | 80.0 |
II | 68.0 | 87.4 | 49.6 | |
III | 56.3 | 86.3 | 48.1 | |
FEMALE | I | 93.5 | 96.1 | 69.8 |
II | 72.2 | 94.1 | 47.9 | |
III | 62.6 | 94.1 | 42.7 |
Conclusions
We have identified a potential PRS that improves classification of melanoma patients within prognostic groups.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Instituto de Salud Carlos III.
Disclosure
All authors have declared no conflicts of interest.
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