Zhou Yi, Wang Chen, Chen Yifang, Zhang Wei, Fu Zailin, Li Jianbo, Zheng Jie, Xie Minghua
Department of Pharmacy, First People's Hospital of Linping District, Hangzhou, Zhejiang, China.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Front Pharmacol. 2023 Jan 16;13:1090857. doi: 10.3389/fphar.2022.1090857. eCollection 2022.
Cutaneous melanoma (CM) is a highly aggressive malignancy with a dimal prognosis and limited treatment options. Anoikis is believed to involve in the regeneration, migration, and metastasis of tumor. The exact role of anoikis-related genes (ARGs) in the development and progression of cutaneous melanoma, however, remains elusive. Four ARGs (, , , and ) with significant differential expression were selected through Cox regression and LASSO analyses. Data for internal and external cohorts validated the accuracy and clinical utility of the prognostic risk model based on ARGs. The Kaplan-Meier curve indicated a much better overall survival rate of low-risk patients. Notably, we also found that the action of ARGs in the CM was mediated by immune-related signaling pathways. Consensus clustering and TIME landscape analysis also indicated that the low-risk score patients have excellent immune status. Moreover, the results of immunotherapy response and drug sensitivity also confirmed the potential implications of informing individualized immune therapeutic strategies for CM. Collectively, the predictive risk model constructed based on ARGs provides an excellent and accurate prediction tool for CM patients. This present research provides a rationale for the joint application of targeted therapy and immunotherapy in CM treatment. The approach could have great therapeutic value and make a contribution to personalized medicine therapy.
皮肤黑色素瘤(CM)是一种侵袭性很强的恶性肿瘤,预后不良且治疗选择有限。失巢凋亡被认为与肿瘤的再生、迁移和转移有关。然而,失巢凋亡相关基因(ARGs)在皮肤黑色素瘤发生发展中的具体作用仍不清楚。通过Cox回归和LASSO分析筛选出四个差异表达显著的ARGs(、、和)。内部和外部队列的数据验证了基于ARGs的预后风险模型的准确性和临床实用性。Kaplan-Meier曲线显示低风险患者的总生存率更高。值得注意的是,我们还发现ARGs在CM中的作用是由免疫相关信号通路介导的。共识聚类和肿瘤免疫微环境(TIME)景观分析也表明低风险评分患者具有良好的免疫状态。此外,免疫治疗反应和药物敏感性的结果也证实了为CM患者制定个体化免疫治疗策略的潜在意义。总体而言,基于ARGs构建的预测风险模型为CM患者提供了一个优秀且准确的预测工具。本研究为CM治疗中联合应用靶向治疗和免疫治疗提供了理论依据。该方法可能具有巨大的治疗价值,并为个性化药物治疗做出贡献。