摘要
Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seve
基金
National Natural Science Foundation of China (81573959)
Capital Health Development Research Special Project (2020-2-4193)。
