The fatty acid-related gene signature stratifies poor prognosis patients and characterizes TIME in cutaneous melanoma

• DOI: 10.1007/s00432-023-05580-7
• Publication Date: 2024-01-27T10:02:23Z
• Authors: Shan Hua; Wenhao Wang; Zuochao Yao; Jiawei Gu; Hongyi Zhang; Jie Zhu; Zhiwen Xie; Hua Jiang
• Keywords: Gene signature; Lasso

Abstract Background The aim of this study is to build a prognostic model for cutaneous melanoma (CM) using fatty acid-related genes and evaluate its capacity predicting prognosis, identifying the tumor immune microenvironment (TIME) composition, assessing drug sensitivity. Methods Through analysis transcriptional data from TCGA-SKCM GTEx datasets, we screened differentially expressed acids-related (DEFAGs). Additionally, employed clinical GSE65904 identify associated with prognosis. Subsequently, utilizing all identified prognosis-related acid genes, performed unsupervised clustering ConsensusClusterPlus R package. We further validated significant differences between subtypes through survival pathway analysis. To predict developed LASSO-Cox signature. This signature's predictive ability was rigorously examined multivariant Cox regression, analysis, ROC curve Following this, constructed nomogram based on aforementioned signature evaluated accuracy utility calibration curves, cumulative hazard rates, decision Using signature, stratified cases into high- low-risk groups compared in characteristics treatment responsiveness these two subgroups. study, provided preliminary confirmation pivotal role CD1D TIME CM. analyzed expression across various cell types correlation intercellular communication single-cell GSE139249 dataset. Results In total 84 DEFAGs were identified, among which 18 Utilizing categorized three subtypes. Significant observed terms outcomes, DEFAGs, proportions, enriched pathways. A regression leading development comprising 6 DEFAGs. Risk scores calculated cases, dividing them high-risk groups. High-risk patients exhibited significantly poorer prognosis than patients, both training group ( p < 0.001) test = 0.002). Multivariate indicated that could independently outcomes [HR 2.03 (1.69–2.45), 0.001]. area under 0.715 0.661, respectively. Combining risk factors including metastatic status patient age, constructed, demonstrated power 3 5 years outcomes. Furthermore, high subgroups displayed composition cells, M1 macrophages, M0 CD8 + T cells. subgroup higher StromalScore, ImmuneScore, ESTIMATEScore better therapy PD1-positive CTLA4-negative or positive expressions 0.001). gene found be mainly monocytes/macrophages dendritic cells within TIME. it enhanced signal transductions other monocytes/macrophages, particularly (HLA-A/B/C/E/F)-CD8A signaling natural killer (NK) 0.01). Conclusions six exhibits strong capabilities TIME, can aid stratification provide guidance strategies. our research highlights crucial CM's laying theoretical foundation future related studies.