皮肤黑色素瘤（SKCM）早期发现率低，死亡率高。现有治疗药物存在许多副作用和药物耐受问题。目前的研究已经确认SKCM病因相关基因促进了皮肤黑色素瘤的侵袭和转移，但它们在肿瘤微环境（TME）中的作用仍不清楚。网络药理学为药物再利用和重新定位提供了新机会，是一种快速、安全、廉价的药物发现方法，可寻找用于SKCM治疗的新药物。本研究基于三个数据库（KEGG、OMIM和Genotype）获取SKCM相关基因和TCGA SKCM数据集，通过对GSE3189和GSE46517的SKCM差异基因进行交集分析，确定SKCM病因相关差异基因，并进行免疫浸润和分析，构建预后算术风险模型进行风险分层和预测，并重点关注ZC3H12A的差异表达及其对TME的影响。最后，采用蛋白质相互作用网络方法量化684个药物靶点与皮肤黑色素瘤之间的相似度，并筛选出与皮肤黑色素瘤相似的药物。基于KEGG、OMIM和Genotype三个数据库，获取了294个SKCM相关基因和18个SKCM病因相关差异基因，其中18个SKCM病因相关差异基因与TME显著相关。构建的预后算术风险模型预测表现更好，为免疫治疗提供了有价值的信息。多元Cox回归分析和K-M分析显示，ZC3H12A是影响SKCM预后的差异表达基因，促进了抗肿瘤免疫细胞CD8 ++T细胞、B细胞和DC细胞的浸润。基于蛋白质相互作用网络方法的分析发现，有43个药物在SKCM治疗中具有高潜力，这43个药物的文献搜索后，发现21个药物已被证实可用于SKCM的治疗。综上所述，与SKCM病因相关的差异基因在肿瘤免疫微环境、临床病理特征和预后中具有重要作用，特别是ZC3H12A在鉴定早期SKCM患者中具有潜在作用。同时，它为SKCM的药物开发提供了新策略，并为SKCM药物的再利用提供了依据。 ©2023. 作者授予Springer-Verlag GmbH Germany的独家许可，隶属于Springer Nature的一部分。

Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 databases (KEGG, OMIM, and Genotype) to obtain SKCM-related genes, and TCGA SKCM dataset, SKCM differential genes in GSE3189 and GSE46517 were intersected to identify SKCM pathogenesis-related differential genes, and the differential genes were immune infiltration and analysis, For survival analysis, a prognostic nomogram risk model was constructed based on the results of multivariate Cox regression analysis for risk stratification and prognosis prediction, then focused on the differential expression of ZC3H12A and its effect on TME. Finally, the protein interaction network method was used to quantify the similarity between 684 drug targets and skin melanoma, and to screen out drugs similar to skin melanoma. Based on 3 databases of KEGG, OMIM, and Genotype, 294 SKCM-related genes and 18 SKCM pathogenesis-related differential genes were obtained, and 18 SKCM pathogenesis-related differential genes were significantly correlated with TME. The constructed prognostic nomogram risk model predicted performance better and provided valuable information for immunotherapy. Multivariate Cox regression analysis and K-M analysis showed that ZC3H12A was a differentially expressed gene affecting the prognosis of SKCM and promoted the infiltration of anti-tumor immune cells CD8 + T cells, B cells, and DC cells. Based on the analysis of the protein interaction network method, 43 drugs were found to have high potential in the treatment of SKCM, and the literature search of these 43 drugs was carried out, and 21 drugs were found to have experimental verification for the treatment of SKCM. Taken together, the differential genes associated with the pathogenesis of SKCM have important roles in the tumor immune microenvironment, clinicopathological features, and prognosis, especially ZC3H12A has a potential role in identifying early SKCM patients. At the same time, it provides a new strategy for the drug development of SKCM and provides a basis for the reuse of SKCM drugs.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.