Identification of Multiple Prognostic Biomarker Sets for Risk Stratification in SKCM

Shivani MalikRitu TomerAkanksha AroraGajendra PS Raghava^*

• Indraprastha Institute of Information Technology Delhi, Delhi, India

Most of the existing studies have identified a single profile of prognostic biomarkers for predicting high-risk cancer patients using transcriptomics data. In this study, we propose multiple distinct sets of prognostic biomarkers for predicting high-risk Skin Cutaneous Melanoma (SKCM) patients. Our primary analysis reveals that the expression of certain genes, such as CREG1, PCGF5, and VPS13C, strongly correlates with overall survival (OS) in SKCM patients. We developed machine learning-based prognostic models to predict 1-, 3-, and 5-year overall survival using gene expression profiles. State-of-the-art feature selection techniques were employed to identify the primary prognostic biomarkers set consisting of 20 genes. Machine learning models built to predict high-risk patients using this set of biomarkers and achieved an AUC of 0.90 and a Kappa of 0.58 in distinguishing high-risk SKCM patients. Similarly, a second independent set of 20 prognostic genes was identified, with no overlap with the primary set. The best model trained on this second set achieved an AUC of 0.89 with a Kappa of 0.56, while the fifth biomarker set achieved the highest performance with an AUC of 0.91 and a Kappa of 0.64. This process was repeated to obtain a total of seven distinct prognostic biomarker sets, each containing 20 unique genes. The predictive performance of these models varied between 0.84 and 0.91 for AUC and 0.48 to 0.64 for Kappa on the test dataset. These findings demonstrate that it is possible to identify multiple independent sets of prognostic biomarkers, each capable of accurately predicting high-risk SKCM patients. We validated a subset of genes from our primary and third prognostic biomarker sets on the independent GEO dataset GSE65904, achieving AUCs of 0.83 and 0.86, respectively. This confirms the predictive value of our biomarkers. All data and code are available at https://github.com/raghavagps/skcm_prognostic_biomarker.