皮肤黑色素瘤（SKCM）是一种高度侵袭性的疾病，晚期肿瘤的预后较差。失巢凋亡是一种由细胞外基质（ECM）脱离触发的半胱天冬酶依赖性细胞死亡过程，可纠正脱离诱导的损害细胞存活的代谢缺陷，最近的研究揭示了失巢凋亡对于癌细胞在转移过程中存活的关键作用。然而，关于失巢凋亡在 SKCM 中的作用的研究有限。我们的研究利用 27 个失巢凋亡相关基因（ARG）将 SKCM 患者分为两个簇，并获得每个簇的差异表达基因（DEG）。这些 DEG 用于逐步 Cox 回归分析，以开发 SKCM 患者的预测模型，该模型由 9 个 ARG 组成，称为失巢凋亡相关特征 (ARS)。随后，我们使用 ARS 计算出的风险评分将 SKCM 患者分为两组，并探讨各组之间免疫微环境、免疫检查点反应性和药物敏感性的差异。确定了 9 个 ARG，将 SKCM 患者分为两个风险组：高危组的预后较差，免疫细胞浸润受到抑制。此外，在低风险组中观察到免疫检查点分子的表达较高以及对免疫治疗和化疗药物的敏感性较高。最后，发现所有 ARS hub 基因在 SKCM 组织和细胞系中均上调。鉴定出一种新的 ARG 特征用于预测 SKCM 的预后。根据我们研究中发现的与 ARS 相关的免疫图谱，针对 ARS 中枢基因可能是 SKCM 的一种有前途的治疗方法。© 2023。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Skin cutaneous melanoma (SKCM) is a highly aggressive disease with a poor prognosis for advanced tumors. Anoikis is a caspase-dependent cell death process triggered by extracellular matrix (ECM) detachment, rectifies detachment-induced metabolic defects that compromise cell survival, recent study revealed the crucial role of anoikis for cancer cells to survive during metastasis. However, limited research focused on the role of anoikis in SKCM.Our study utilized the 27 anoikis-related genes (ARGs) to divide SKCM patients into two clusters, and obtain differentially expressed genes (DEGs) for each cluster. These DEGs were used in stepwise Cox regression analysis to develop a prediction model for SKCM patients consisting of nine ARGs, called the anoikis-related signature (ARS). Subsequently, we used the risk scores calculated from the ARS to divide SKCM patients into two groups and explored differences in immune microenvironment, immune checkpoint reactivity, and drug sensitivity between the groups.Nine ARGs were identified to stratify SKCM patients into two risk groups, patients in the high-risk group had a poor prognosis and suppressed immune cell infiltration. Moreover, higher expression of immune checkpoint molecules and a greater sensitivity to immunotherapy and chemotherapy drugs were observed in the low-risk group. Finally, all of the ARS hub genes were found to be upregulated in SKCM tissues and cell lines.A novel ARGs signature was identified for predicting the prognosis of SKCM. Based on the immune landscape associated with ARS discovered in our study, targeting ARS hub genes may be a promising treatment for SKCM.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.