Abstract
Background: Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical. Methods: In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed. Results: Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction. Conclusion: The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.
Highlights
Pancreatic adenocarcinoma (PAAD) is an aggressive gastrointestinal malignancy, with a high mortality rate (Mizrahi et al, 2020)
Gene expression data and clinical information were downloaded from the The Cancer Genome Atlas (TCGA)-PAAD cohort FPKM file from the TCGA Information Portal
The ferroptosis-related mRNAs were obtained from the FerrDb database, which comprised a total of 239 genes
Summary
Pancreatic adenocarcinoma (PAAD) is an aggressive gastrointestinal malignancy, with a high mortality rate (Mizrahi et al, 2020). Emerging evidence suggests that ferroptosis provides a link between the pathophysiological disease mechanism and the altered human health status through its involvement in metabolic and redox reactions and negatively affects (Zheng and Conrad, 2020). It is promoted by BRCA1-associated protein 1 (BAP1) through SLC7A11 repression, and inhibited by glutathionedependent phospholipid peroxidase 4, preventing lipid peroxide accumulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical
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