Construction of a prognostic risk model for lung adenocarcinoma based on cuproptosis-related lncRNAs signature and the experimental validation

JIAN Ruonan; ZHEN Hua; YANG Lei; GUO Jingjing

doi:10.3969/j.issn.1674-3806.2025.01.10

Abstract：Objective To construct a prognostic risk model for lung adenocarcinoma based on cuproptosis-related long non-coding RNAs(lncRNAs)signature and to verify the model by experiment.Methods The lung adenocarcinoma data were obtained from The Cancer Genome Atlas(TCGA)database to construct the prognostic risk model of cuproptosis-related lncRNAs signature(CRLS)and risk scores were calculated,and the patients were divided into high-risk group(≥the median of risk scores)and low-risk group(＜the median of risk scores)according to the median.Risk score distribution curves and scatter plots were used to show the relationship between risk scores and survival status,and the predictive efficacy was assessed by using principal component analysis(PCA),Kaplan-Meier analysis and C-index curve.The sensitivities to different drugs were assessed in both groups by using Tumor Drug Sensitive Multiomics Library,and the sensitivities to immune checkpoint inhibitors(ICIs)were compared between the two groups by using the Tumor Immune Dysfunction and Exclusion algorithms(TIDE).Cancer susceptibility candidate 15(CASC15)was selected for cellular experiments and was transfected into A549 and H1975 cells,and the cell expression,proliferation and invasion ability were assessed by using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),CCK-8 and Transwell assay.Results Seven CRLS were finally screened to be significantly associated with overall survival(OS),with risk scores=-0.308 1 × AC090948.1 expression+0.460 4 × CASC15 expression-0.417 0 × AL353804.1 expression-1.432 2 × AP000302.1 expression+0.441 7 × AC026356.1 expression-0.619 0 × AC007613.1 expression+0.271 0 × AL161431.1 expression.As the risk scores increased,the number of patients who died increased.The constructed risk model was able to effectively differentiate between low-risk patients and high-risk patients,and the survival prognosis of the low-risk group was better than that of the high-risk group(log-rank test:x2=29.352,P＜0.001).The conformity index of the risk scores was higher than that of the age,gender,and clinical stage,and the predictive accuracy of the risk scores was better.The IC50 values of cisplatin,paclitaxel,docetaxel,5-fluorouracil,vinorelbine,camptothecin,gemcitabine,gefitinib and ceritinib in the high-risk group were lower than those in the low-risk group,and the IC50 values of erlotinib and rapamycin in the high-risk group were higher than those in the low-risk group,and the differences were statistically significant(P＜0.05).The TIDE scores of the low-risk group were lower than those of the high-risk group,and the differences were statistically significant(P＜0.05).Cellular experiments showed that the cell proliferation rate,the clone formation rate and cell invasion rate in the CASC15 group were significantly increased compared with those in the blank group and the control group(P＜0.05).Conclusion The risk model consisting of 7 CRLS can effectively predict the survival prognosis of lung adenocarcinoma patients,and risk score of the model can be used as an independent prognostic factor.The model provides a new theoretical basis for lung adenocarcinoma patients to choose conventional drugs or immunotherapy.