Abstract
Background: Breast cancer is the most common cancer in women globally. LncRNAs are non-coding RNAs that play an essential role in biological pathways. Many lncRNAs have been discovered to influence cancer medication resistance. As a result, identifying how lncRNAs may cause drug resistance is vital.Method: Breast cancer TCGA RNA-seq data was applied in this study. We used the PharmacoGX package to explore lncRNAs with drug resistance or sensitivity effect through GDSC and CCLE data. Differential gene expression analysis (DGE) was used to find dysregulated lncRNAs (P<0.01). Survival analysis was performed to identify lncRNAs associated with patient survival, and a model based on them was developed. Multivariate cox regression analysis and ROC curve analysis were applied to assess the model. The TCGA-BRCA and two independent datasets (GSE21653 and GSE20685) were used to study the relevance of lncRNAs in biological pathways. lncRNA-miRNA-mRNA interaction network was investigated. The connections of lncRNAs with MRPs were analysed through the correlation test. Finally, lncRNA and MRP mRNAs attachment sites were analysed through the LncRRisearch tool.Result: According to our data, thirty-eight lncRNAs were associated with cell drug response in breast cancer cells. IL12A-AS1, AC137723.1, LINC00667, SVIL-AS1, CYTOR, and MIR4435-2HG linked to patient survival (P<0.05). AC137723.1 and LINC00667 were identified as good prognostic genes, while the others were discovered to have poor prognostic effects. Moreover, the risk score model separated patients perfectly, in which about 45% of high-risk patients were dead; by contrast, around 95% of low-risk patients could survive. ROC curve results proved that CYTOR, MIR4435-2HG, and LINC00667 are potential biomarkers in breast cancer with AUC >0.8. Pathway analysis revealed that CYTOR and MIR4435-2HG are highly correlated with the Epithelial-Mesenchymal transition pathway, while AC137723.1 and LINC00667 were negatively correlated with the pathway. AC128688.2, CYTOR, TDRKH-AS1 and LINC00667 can participate in lncRNA-miRNA-mRNA networks. Also, MIR22HG might influence drug resistance by attaching to MRP mRNAs.Conclusion: Our findings revealed 38 lncRNAs involved in cancer cell treatment resistance and sensitivity. They can participate in patients’ prognosis, diagnosis and cellular pathways. Also, they may influence cell drug response through connections with CSPs, lncRNA-miRNA-mRNA networks and MRPs.