Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma

作者：Yi Geng, Yu-jie Sun, Hao Song, Qiu-Ju Miao, Yifei Wang, Jinliang Qi, Xiu-Lian Xu, Jianfang Sun · 发表于：Clinical Cosmetic and Investigational Dermatology · 年份：2023 · DOI：10.2147/ccid.s410723 · 被引用次数：7 · 研究领域：Inflammasome and immune disorders、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

Background: Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear. Objective: To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients. Methods: Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature's independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples. Results: The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activat...