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.
Highlights
Pancreatic cancer (PC) is one kind of the most devastating carcinoma worldwide (Vincent et al, 2011)
Ferroptosis, an extraordinary cell death pathway driven by irondependent lipid peroxidation, regulates the epigenetic program and metabolic changes in numerous cancers (Wu et al, 2020)
Multiple studies have already shown that specific Long non-coding RNA (lncRNA) can alleviate the malignancy of tumors by regulating the ferroptosis-related pathway
Summary
Pancreatic cancer (PC) is one kind of the most devastating carcinoma worldwide (Vincent et al, 2011). Ferroptosis-Related Biomarker in PC expression and mutation of lncRNAs serve a crucial part in the malignant proliferation of PC (Xiong et al, 2017; Sun and Ma, 2019). PLACT1 was previously reported to be an E2F1-mediated lncRNA promoting pancreatic ductal adenocarcinoma (PDAC) tumorigenicity and metastatic potential (Ren et al, 2020); THAP9-AS1 was considered as a potential biomarker to play an essential role in PDAC growth via enhancing YAP signaling (Li et al, 2020), and overexpression of GSTM3TV2 could strengthen the chemoresistance in PC (Xiong et al, 2019). Few studies have focused on the mechanisms of how ferroptosis regulates the development and advance in lncRNA-mediated PC. On that account, fathoming out the relationship between ferroptosis of lncRNA and PC development is urgently needed to detect novel prognostic signatures that can behave as effective targets for treatment
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