A stratification system of ferroptosis and iron-metabolism related LncRNAs guides the prediction of the survival of patients with esophageal squamous cell carcinoma

Abstract

Ferroptosis and iron-metabolism have been widely reported to play an important role in cancer. Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in esophageal squamous cell carcinoma (ESCC) is essential for prognosis prediction. Herein, Pearson's correlation analysis was carried out between ferroptosis and iron-metabolism-related genes (FIRGs) and all lncRNAs to derive the FIRLs. Based on weighted gene co-expression network exploration (WCGNA), least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis, a risk stratification system, including 3 FIRLs (LINC01068, TMEM92-AS1, AC243967.2), was established. According to Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and univariate and multivariate Cox regression analyses, the risk stratification system had excellent predictive ability and clinical relevance. The validity of the established prognostic signature was further examined in TCGA (training set) and GEO (validation set) cohorts. A nomogram with enhanced precision for forecasting OS was set up on basis of the independent prognostic elements. Functional enrichment analysis revealed that three FIRLs took part in various cellular functions and signaling pathways, and the immune status was varied in the high-risk and low-risk groups. In the end, the oncogenic effects of LINC01068 was explored using in vitro researches. Overall, a risk stratification system of three FIRLs was found to have significant prognostic value for ESCC and may serve as a ferroptosis-associated therapeutic target in the clinic.

Identifying Ferroptosis‐Related Genes Associated with Weight Loss Outcomes and Regulation of Adipocyte Microenvironment

“…This dataset was screened for 330 DEGs. And we identified phosphoGlycerol dehydrogenase(PHFDH), [ 26 ] C‐C motif chemokine receptor 10(CCR10), [ 27 ] transmembrane protein 92(TMEM92), [ 28 ] aldolase,fructose‐bisphosphate C Gene(ALDOC), [ 29 ] and X‐inactive specific transcipt(XIST) [ 30 ] as being significantly upregulated in the PO group, all of which are associated with promoting ferroptosis (Supplemental material S2). DEGs‐based KEGG enrichment analyses showed the enrichment of 20 pathways.…”

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

“…Zhao et al [ 132 ] identified six genes associated with iron metabolism and iron death ( PRNP , SLC3A2 , SLC39A8 , SLC39A14 , ATP6V0A1 , and LCN2 ) in ESCC, and these genes may be associated with the infiltration of immune cells, tumor mutational load and ESCC prognosis. In addition, lncRNAs such as LINC01068, TMEM92-AS1 and AC243967.2 have been reported to be correlated with iron metabolism and iron death, and be closely related to the infiltration of immune cells in ESCC[ 133 ]. Moreover, Zhang et al [ 134 ] reported that mitochondrial energy metabolism is associated with the TIME and poor prognosis in ESCC patients, and identified several fatty acid metabolism-related genes that are predictors of EC prognosis[ 135 ].…”