Research Paper Volume 15, Issue 22 pp 13504—13541

Figure 7. Demonstration of the relationship between the CoCuLncSig and immunotherapy [80]. Correlation between risk score and ICB response signature (A) and correlation between risk score and each step of the tumor immune cycle (B). (C) A waterfall plot displays the mutational landscape of the 20 most frequently mutated genes in LUAD. Furthermore, the plot showcases the variations in mutations of these genes between the high-risk and low-risk LUADs. (D) Boxplots on the left show the difference in the distribution of TMB and TIDE among high-risk and low-risk patients by the Wilcoxon rank sum test. On the right side, scatterplots depict the correlations between risk scores and TMB and TIDE, evaluated by Pearson analysis. (E) The ridgeline plot (left) presents the distribution of risk score variation in nonresponse and response LUADs. The proportion (right) of patients with response and nonresponse to immunotherapy in the high and low CoCuLncSig score groups. (F) Lollipop plots visualize the correlation between CoCuLncSig and immune checkpoints. Correlation was detected by Pearson’s coefficient test. (G) Violin plots showing differences in expression of immune checkpoint genes between high and low risk groups. Differences in expression were analyzed using the Wilcoxon rank sum test. (H) Cox analysis was performed to reveal the prognostic potential of the 60 checkpoint genes. The Cox results showed that 15 checkpoint genes had prognostic ability. (I) KM analysis evaluated whether high-expression and low-expression checkpoint genes had the predictive ability for LUAD outcomes. The KM results demonstrated that 8 out of 60 checkpoint genes could discriminate LUAD prognosis. (J) The Venn diagram merges findings from correlation analysis, difference distribution analysis, Cox analysis, and KM analysis to identify the checkpoint genes associated with CoCuLncSig and impacting the prognosis of LUAD. (K) A heatmap has been generated to display published datasets’ relative immunotherapy scores for six checkpoint genes. The checkpoint genes, ranked in order of their immunotherapy score from high to low, are IL10, IL2, CD40LG, SELP, BTLA, and CD28. The immunotherapy scores have been subjected to zero-mean normalization. CoCuLncSig: copper homeostasis and cuproptosis regulated lncRNA signature; KM: Kaplan–Meier estimator; TMB: Tumor mutational burden; ICB response: immune checkpoint blockers response; TIDE: Tumor Immune Dysfunction and Exclusion; ns: not significant; rSeg: r segment; pSeg: p-value segment; sign: significant; pos: positively; neg: negatively; LUAD: lung adenocarcinoma; Asterisks denote statistical significance levels; in this context, the significance levels for p-values are as follows: ^*p-value < 0.05 ^**p-value < 0.01 ^***p-value < 0.001 ^****p-value < 0.0001; A p value < 0.05 was used as the threshold for statistical significance.