Research Paper Volume 13, Issue 19 pp 23072—23095

Establishment of a novel ferroptosis-related lncRNA pair prognostic model in colon adenocarcinoma

Hong Li1, *, , Lili Liu2, *, , Tianyi Huang3, *, , Ming Jin3, , Zhen Zheng3, , Hui Zhang3, , Meng Ye4, , Kaitai Liu3, ,

  • 1 Department of General Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
  • 2 Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
  • 3 Department of Radiation Oncology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
  • 4 Department of Oncology and Hematology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
* Equal contribution

Received: June 14, 2021       Accepted: September 20, 2021       Published: October 5, 2021      

https://doi.org/10.18632/aging.203599
How to Cite

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be prognostic factors for cancer. Ferroptosis is an iron-dependent process of programmed cell death. Here, we established a ferroptosis-related lncRNA (frlncRNA) pair signature and revealed its prognostic value in colon adenocarcinoma (COAD) by analyzing the data from The Cancer Genome Atlas (TCGA). FrlncRNAs were identified based on co-expression analysis using the Pearson correlation. Differentially expressed frlncRNAs (DEfrlncRNAs) were recognized and paired, followed by prognostic assessment using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) penalized Cox analysis was used to determine and construct a risk score prognostic model, by which the receiver operating characteristic (ROC) curves for predicting the overall survival (OS) were conducted. Following the evaluation of whether it was an independent prognostic factor, correlations between the risk score model and clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants were investigated. In total, 148 DEfrlncRNA pairs were identified, 25 of which were involved in a risk score prognostic signature. The area under ROC curves (AUCs) representing the predictive effect for 1-, 3-, and 5-year survival rates were 0.860, 0.885, and 0.934, respectively. The risk score model was confirmed as an independent prognostic factor and was significantly superior to the clinicopathological characteristics. Correlation analyses showed disparities in clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants, as well as specific signaling pathways between high- and low-risk groups. The novel risk score prognostic model constructed by pairing DEfrlncRNAs showed promising clinical prediction value in COAD.

Abbreviations

LncRNAs: long non-coding RNAs; FrlncRNA: ferroptosis-related lncRNA; COAD: colon adenocarcinoma; TCGA: The Cancer Genome Atlas; LASSO: least absolute shrinkage and selection operator; ROC: receiver operating characteristic; AUCs: area under ROC curves; OS: overall survival; HNSCC: head and neck squamous cell carcinoma; FrGenes: ferroptosis-related genes; TIICs: tumor immune infiltrating cells; ICGs: immune checkpoint genes; TMB: tumor mutation burden; Mb: megabase; HTSeq: high-throughput sequencing; FPKM: fragments per kilobase of transcript per million mapped reads; FDR: false discovery rate; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis.