Fan Xin, Lu Lingyi, Wang Sihan, Zhou Qiongyan, Lin Bingjiang
Department of Dermatology, The First Affiliated Hospital of Ningbo University, 59 Liuting Street, Ningbo, 315010, Zhejiang, China.
School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Sci Rep. 2025 Jul 1;15(1):20650. doi: 10.1038/s41598-025-07829-2.
Necroptosis is a novel programmed cell death that affects the tumor heterogeneity, microenvironment, and prognosis, which is not well elucidated in skin cutaneous melanoma (SKCM). The SKCM-TCGA, GSE65904, and GSE215120 datasets were downloaded from the TCGA and GEO databases, respectively. The necroptosis-related genes were identified by weighted co-expression network analysis (WGCNA) and single-cell sequencing analysis. COX and LASSO regression was used to construct the prognostic model. Survival analysis, immune infiltration analysis, and tumor mutation analysis between the high-necroptosis score (NCPTS) and low-NCPTS groups were performed. Finally, real-time PCR experiment was carried out to verify the results. A prognostic model based on 9 necroptosis-related genes (TUFM, CD53, CLEC2D, KLRC1, STAT4, IFI35, XCL1, TAPBP, and SOD2) was constructed to predict the prognosis of SKCM patients. The patients in high-NCPTS group had a poor prognosis. The expression of immune checkpoint-related gene and drug sensitivity were higher than those in the low-NCPTS groups, indicating susceptible for immunotherapy. Real-time PCR showed that TUFM expression was significantly higher in A375 cells than control (P < 0.05). Besides, TUFM expression was also validated by TISCH and HPA database. The prognostic model might provide guidance for the prognosis and immunotherapy for SKCM patients, contributing to a better understanding of necroptosis in SKCM.
坏死性凋亡是一种新型程序性细胞死亡,它影响肿瘤异质性、微环境和预后,而皮肤黑色素瘤(SKCM)中对此尚未有充分阐明。分别从TCGA和GEO数据库下载了SKCM-TCGA、GSE65904和GSE215120数据集。通过加权共表达网络分析(WGCNA)和单细胞测序分析鉴定坏死性凋亡相关基因。使用COX和LASSO回归构建预后模型。对高坏死性凋亡评分(NCPTS)组和低NCPTS组进行生存分析、免疫浸润分析和肿瘤突变分析。最后,进行实时PCR实验验证结果。构建了基于9个坏死性凋亡相关基因(TUFM、CD53、CLEC2D、KLRC1、STAT4、IFI35、XCL1、TAPBP和SOD2)的预后模型,以预测SKCM患者的预后。高NCPTS组患者预后较差。免疫检查点相关基因的表达和药物敏感性高于低NCPTS组,表明对免疫治疗敏感。实时PCR显示,TUFM在A375细胞中的表达明显高于对照组(P < 0.05)。此外,TUFM的表达也通过TISCH和HPA数据库得到验证。该预后模型可能为SKCM患者的预后和免疫治疗提供指导,有助于更好地理解SKCM中的坏死性凋亡。
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