摘要
      皮肤黑色素瘤（SKCM）是一种侵袭性很强、预后很差的疾病，尤其是晚期肿瘤。Anoikis可以防止分离的细胞在错误的位置重新附着到新的基质上，并抑制它们不必要的生长，它在组织防御中发挥着至关重要的作用。然而，很少有研究关注失巢对SKCM预后的影响。为了解决这一问题，我们的研究利用基因集富集分析（GSEA）中鉴定的27个失巢相关基因（ARG）将TCGA-SKCM队列中的SKCM患者分为两个聚类，并获得每个聚类的差异表达基因（DEG）。然后将这些DEG用于逐步Cox回归分析，以开发由9个ARG组成的SKCM患者的预测模型，称为Anoikis相关特征（ARS）。随后，我们使用ARS计算的风险评分将SKCM患者分为两组，并探讨了两组之间在免疫微环境、免疫检查点反应性和药物敏感性方面的差异。我们的研究结果表明，免疫疗法对高ARS患者无效。总之，ARS可用于SKCM患者的风险分类和生存结果预测，为SKCM的靶向治疗提供基础。关键词：皮肤黑色素瘤，失活细胞，免疫反应，风险模型，预后。
Abstract
Skin cutaneous melanoma (SKCM) is a highly aggressive disease with a poor prognosis, especially for advanced tumors. Anoikis, which prevents detached cells from re-attaching to a new substrate in an incorrect location and inhibits their unwanted growth, plays a crucial role in organismal defense. However, little research has focused on the impact of anoikis on prognosis in SKCM. To address this, our study utilized the 27 anoikis-related genes (ARGs) identified from gene set enrichment analysis (GSEA) to divide SKCM patients in the TCGA-SKCM cohort into two clusters, and obtain differentially expressed genes (DEGs) for each cluster. These DEGs were then 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. Our results revealed that immunotherapy was ineffective in patients with high ARS. In summary, the ARS can be used to classify the risk and predict the survival outcome of SKCM patients, providing a basis for targeted therapy in SKCM. Keywords: cutaneous melanoma, anoikis, immune response, risk model, prognosis.

https://www.researchsquare.com/article/rs-2822229/v1