AUTHOR=Song Xuesong , Hou Lin , Zhao Yuanyuan , Guan Qingtian , Li Zhiwen 

TITLE=Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1039499

DOI=10.3389/fphar.2022.1039499

ISSN=1663-9812

ABSTRACT=Background: Gastric cancer is one of the most important malignancies with bad prognosis. Ferroptosis and cuproptosis are newly discovered metal-dependent programmed cell death, which may directly affect the outcome of gastric cancer. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer with stable structure, which could be potential prognostic prediction factors for gastric cancer.
Methods: Differentially expressed metal-dependent PCD related lncRNAs were identified with DESeq2 and Pearson’s correlation analysis. Through GO, KEGG and GSEA analysis, we identified the potential effects of metal-dependent PCD-related lncRNAs towards prognosis. Using COX regression analysis with LASSO method, we constructed a 12 lncRNAs prognostic signature model. And we also evaluated the prognostic efficiency with Kaplan–Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, as well as Decision Curve Analysis (DCA) methods. The sensitivities for anti-tumor drugs and were then predicted with pRRophetic method. And we discuss the Chinese patent medicines and plant extracts which could induce metal-dependent programmed cell death.
Results: We constructed metal-dependent PCD-related lncRNA-genes co-expression network. And a metal-dependent PCD-related gastric cancer prognostic signature model, including 12 lncRNAs was constructed. And K-M survival curve revealed a worse prognosis in high-risk group. ROC curve analysis shown the AUC of our model is 0.766, which was better than other published models. And half-maximum inhibitory concentration (IC50) for dasatinib, lapatinb, sunitinib, cytarabine, saracatinib and vinorelbine were much lower among high-risk group.
Conclusions: Our 12 metal-dependent PCD-related lncRNAs prognostic signature model may improve the OS prediction for gastric cancer. And anti-tumor drug sensitivity analysis results may also helpful for individualized chemotherapy regimens design.