Identification and verification of a prognostic ferroptosis-related lncRNAs signature for patients with lung adenocarcinoma.

Lung cancer has been identified as one of the deadliest malignant tumors worldwide. Mounting evidence suggests that ferroptosis is a well-known non-apoptotic cell death process that participates in pathological mechanisms and is a new cancer treatment strategy. Aberrantly expressed long non-coding RNAs (lncRNAs) that drive lung cancer progression have attracted increasing attention. Herein, we explored the prognostic significance of ferroptosis-related lncRNAs in lung cancer patients. LUAD gene expression patterns and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) database. Based on LASSO-Cox regression, A 14 ferroptosis-related differentially expressed lncRNAs (FRDELs) signature was constructed. Subsequently, a nomogram model for predicting the prognosis of LUAD patients was constructed based on clinicopathological data and the 14 - FRDELs signature. The signature was shown to be correlated with tumor mutational burden (TMB) and immune cell infiltration within the tumor microenvironment. Furthermore, Gene Set Enrichment Analysis (GSEA) confirmed that the signature was correlated with LUAD-related biological functions such as the P53 signaling pathway, DNA replication, and cell cycle. The roles and mechanisms of PACERR in the signature were explored by si-lncRNA-mediated knockdown and transfection-mediated overexpression via in vitro experiments in A549 and H1299 cells. PACERR was significantly upregulated in A549 and H1299 cells, and higher expression promoted LUAD cell proliferation, migration, and invasion via in vitro experiments, while knockdown of PACERR presented the opposite effects. In conclusion, our study provided information regarding ferroptosis-related lncRNA expression and established a prognostic nomogram based on 14 FRDELs to predict overall survival in LUAD accurately. Additionally, our results in vitro revealed that PACERR played an oncogenic role in LUAD proliferation and metastasis, which provides mechanistic insights into the roles of ferroptosis-related lncRNA in LUAD progression and that it may be a potential biomarker for LUAD treatment. AJTR