Construction and Validation of a Seven-Gene Signature for Predicting Prognosis and treatment response of Melanoma Based on Parkinson's Disease Family Genes

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Abstract Parkinson's disease (PD) patients generally have a lower cancer risk, except for an increased melanoma risk, suggesting a link between PD genes and melanoma development.However, comprehensive research on the expression and function of the Parkinson's gene family in melanoma is currently lacking. Here, this study aimed to explore the expression of Parkinson's genes in melanoma and their predictive value for prognosis and treatment response will aid in the development of new diagnostic and therapeutic markers for melanoma. Using LASSO regression analysis, we obtained a seven Parkinson's genes signature melanoma prognosis model, including LRRK2, UCHL1, SNCA, VPS13C, SPR, EIF4G1, and FBXO7. Subsequently, internal verification with TCGA cohort and external verification with GEO cohort showed that the seven-gene prognostic model could effectively predict the prognosis for patients with melanoma. Paitents with high risk score had worse overall survival than those with high risk score. The signaling pathways related to anti-tumor immunity, such as interferon α/γ, were significantly activated in the low-risk group. Cancer-related signaling pathways are mainly enriched in high-risk group, such as mTOR, WNT/β-catenin, and Notch pathways. Moreover, low-risk melanoma patients have a higher infiltration of CD8+ T, cytotoxic, and Th1 cells within the tissue as compared with high-risk patients. Melanom patients in the low-risk group had a higher response rate and longer survival after PD-1 treatment, and were more sensitive to drug treatment, such as Nilotinib. We have successfully constructed a 7-gene signature based on Parkinson's disease familial genes, which can efficiently predict the prognosis of melanoma and treatment response.

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