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.

Keywords

• colorectal cancer
• ferroptosis
• long non-coding RNA
• prognostic signature
• metastasis