Integrated Analysis of a Ferroptosis-Related LncRNA Signature for Evaluating the Prognosis of Patients with Colorectal Cancer

Abstract

LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. However, the functions and clinical implications of ferroptosis-associated lncRNAs in CRC remain largely unknown. We, herein, aim to construct a prognostic signature with ferroptosis-related lncRNAs for the prognostic estimation of CRC patients. Firstly, we identified the lncRNAs related to ferroptosis based on the RNA-Seq data of CRC from the TCGA database. The univariate and multivariate Cox analyses were then performed to establish a prognostic signature composed of eight ferroptosis-related lncRNAs (AL161729.4, AC010973.2, CCDC144NL-AS1, AC009549.1, LINC01857, AP003555.1, AC099850.3, and AC008494.3). Furthermore, we divided the CRC patients into high- and low-risk groups based on the signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that in the low-risk group (p = 3.31 × 10−11). Moreover, the patients in the high-risk groups had shorter recurrence-free survival (RFS) (p = 6.5 × 10−3) and disease-free survival (DFS) (p = 4.27 × 10−4), as well as higher tumor recurrence rate. Additionally, we found that the oncogenic pathways were enriched in the high-risk group, whereas the ferroptosis pathway that probably repressed CRC development was enriched in the low-risk group. In summary, our signature may provide a theoretical foundation for not only accurate judgment for prognosis but also evaluation for recurrence and metastasis in CRC patients.

Construction of a Prognostic Model for Predicting Colorectal Cancer Prognosis and Response to Immunotherapy Based on Cuproptosis-Associated lncRNAs

“…A variety of studies showed that prognostic models based on lncRNAs have guiding significance for patient prognosis [ 23 ]. Therefore, the purpose of this study is to establish a CRLs-based model to facilitate the prognostic prediction of CRC.…”

Tracing vitamins on the long non-coding lane of the transcriptome: vitamin regulation of LncRNAs

“…However, alpha-tocopherol can prevent ferroptosis, a type of iron-dependent programmed cell death associated with blood and neurological diseases, ischemia–reperfusion injury, kidney injury, inflammation, and cancer [ 74 ]. Ferroptosis-related lncRNAs have been reported in a wide range of cancers, including hepatocellular carcinoma [ 75 ], head and neck squamous cell carcinoma [ 76 ], colorectal cancer [ 77 ], and stomach adenocarcinoma [ 78 ]. Future studies are expected to define vitamin E/ferroptosis-related lncRNAs axes [ 79 ].…”

Immune landscape of a prognostic immunogenic cell death (ICD)-related long noncoding RNAs (lncRNAs) signature in colon adenocarcinoma (COAD)

“…LINC02257, as an enhancer RNA, was signi cantly correlated with unfavorable prognosis of COAD patients [31]. Xu et al reported AL161729.4, as a ferroptosis-related lncRNA, was a risk factor for colorectal cancer [32]. A pyroptosis-related lncRNA signature for bladder cancer and differential analysis of lncRNA signature in esophageal cancer displayed the prognostic values of AC007128.1 [33,34].…”