Research Paper Volume 15, Issue 22 pp 13504—13541

Figure 5. The stability and applicability of CoCuLncSig were validated in the study cohorts. (A) The prognostic value of CoCuLncSig was demonstrated through Kaplan-Meier analysis in both the training and validation cohorts, which also affirms its broad applicability. By using their median CoCuLncSig risk scores, patients were stratified into high- and low-risk groups, and Kaplan-Meier analysis revealed significant differences in survival between the two groups. (B) Univariate and multivariate Cox proportional hazards models were built, incorporating risk scores and several clinical variables. ^#: the types of variables involved in the studied cohorts. The types of variables included in the analysis were defined as follows: Gender (male vs. female), Race (white vs. non-white), Ethnicity (Hispanic or Latino vs. non-Hispanic or Latino), Prior malignancy (yes vs. no), Tumor origin (upper lobe lung vs. non-upper lobe lung), and Smoking history (ever vs. never). (C) ROC curves. Our signature’s accuracy in predicting LUAD outcomes at 1-year, 3-year, and 5-year intervals was evaluated using ROC curves. (D) The purpose of the tAUC analysis was to continually assess the prognostic precision of our signature relative to other clinical measures over successive time intervals. An increase in the AUC size is indicative of a more robust predictive accuracy of the model. (E) The principal component analysis visualization clearly indicates that the signature is capable of distinguishing the LUAD population. (F) A nomogram model was created that predicts the clinical outcome of LUAD patients using seven factors: risk score, tumor stage, age, grade, smoking history, prior malignancy, and tissue origin. This model forecasts the overall survival of patients for 1, 3, and 5 years in the TCGA-LUAD cohort. The significance of the results was indicated using asterisks, where ^* represents a p-value of < 0.05 and ^*** represents a p-value of < 0.001. (G) 1-, 3-, and 5-year overall survival calibration plots for LUAD patients based on the predictive nomogram model. These plots depict the predicted survival rate on the X-axis and the actual survival rate of LUAD patients on the Y-axis. The 45° line on the graph indicates the optimal predicted value. A curve that closely follows the 45° line indicates better results. (H) The GSEA analysis identified 10 KEGG pathways with the strongest association with CoCuLncSig. These pathways’ significance thresholds were established as p-value < 0.05 and FDR < 0.25. CoCuLncSig: copper homeostasis and cuproptosis regulated lncRNA signature; L95: 95% confidence interval lower; H95: 95% confidence interval higher; HR: hazard ratio; AUC: area under the ROC curve; ROC: receiver operating characteristic; tAUC: time-dependent AUC; TCGA: The Cancer Genome Atlas; GSEA: Gene Set Enrichment Analysis; LUAD: lung adenocarcinoma; OS: overall survival; KEGG: Kyoto Encyclopedia of Genes and Genomes; FDR: false discovery rate; A statistical significance was deemed to be present when the P-value was less than 0.05.