Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Abstract

Pancreatic cancer (PC) is one of the most lethal malignancies, the mortality and morbidity of which have been increasing over the past decade. Ferroptosis, a newly identified iron-dependent cell death pattern, can be induced by iron chelators and small lipophilic antioxidants. Nonetheless, the prognostic significance of ferroptosis-related lncRNAs in PC remains to be clarified. We obtained the lncRNA expression matrix and clinicopathological information of PC patients from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) datasets in the current study. Firstly, we conducted Pearson correlation analysis to delve into the ferroptosis-related lncRNAs, and univariate Cox analysis was implemented to examine the prognostic values in PC patients. Twenty-three prognostic ferroptosis-related lncRNAs were confirmed and loaded into the least absolute shrinkage and selection operator Cox (LASSO-Cox) analysis, then a ferroptosis-related lncRNA prognostic marker (Fe-LPM) was established in the TCGA dataset. Risk scores of patients were calculated and segregated PC patients into low-risk and high-risk subgroups in each dataset. The prognostic capability of Fe-LPM was also confirmed in the ICGC dataset. Gene set enrichment analysis (GSEA) revealed that several ferroptosis-related pathways were enriched in low-risk subgroups. Furthermore, we adopted a multivariate Cox regression to establish a nomogram based on risk score, age, pathological T stage and primary therapy outcome. A competing endogenous RNA (ceRNA) network was also created relied on four of the twenty-three ferroptosis-related lncRNAs. In conclusion, the eight Fe-LPM can be utilized to anticipate the overall survival (OS) of PC patients, which are meaningful to guiding clinical strategies in PC.

Development and validation of a novel ferroptosis‑related lncRNA prognostic signature for pancreatic adenocarcinoma

“…In previous studies, several prognostic models have also been constructed based on lncRNAs to assess the prognosis of patients with PAAD. Chen et al ( 71 ) constructed an evaluation model based on ferroptosis-related lncRNAs, and the AUC values were 0.70 at 1 year, 0.71 at 3 years and 0.75 at 5 years, which were lower than those for the model developed in the present study. In another study, Shi et al ( 72 ) reported a prognostic three lncRNA signature, and the AUC of this model was 0.716.…”

“…The AUC values at 2 and 3 years slightly decreased compared with 1 year. Several other prognostic models also reported a decrease in the AUC values at 2 and 3 years ( 71 , 74 , 75 ). Numerous factors affect the AUC value and one of the important factors is the uncertainty of the sample.…”

Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death?

“…Their study demonstrated that ferroptosis-related long noncoding RNAs are prognostic biomarkers for patients with PDAC by utilizing SLC16A1-AS1, SETBP1-DT, ZNF93-AS1, SLC25A5-AS1, AC073896.2, LINC00242, PXN-AS1, and AC036176. It was found that the low-risk subgroup is enriched in ferroptosis-related pathways (fatty acid metabolism and oxidative phosphorylation), the survival cancer pathway (PI3K-AKT-mTOR signaling), and organelles (peroxisome and lysosome) [60]. Considering these studies, there appears to be a connection among genomes, the metabolism, signaling pathways, and immune systems, which is further explored in the following sections.…”