Identification and Validation of Ferroptosis-Related LncRNAs Signature as a Novel Prognostic Model for Chronic Lymphocytic Leukemia

Zhangdi Xu; Bihui Pan; Yue Li; Yi Xia; Jinhua Liang; Yilin Kong; Xinyu Zhang; Jing Tang; Li Wang; Jianyong Li; Wei Xu; Jiazhu Wu

doi:10.2147/IJGM.S399629

Identification and Validation of Ferroptosis-Related LncRNAs Signature as a Novel Prognostic Model for Chronic Lymphocytic Leukemia

Int J Gen Med. 2023 Apr 26:16:1541-1553. doi: 10.2147/IJGM.S399629. eCollection 2023.

Authors

Zhangdi Xu^#^{1

2

3}, Bihui Pan^#^{1

2

3}, Yue Li^{1

2

3}, Yi Xia^{1

2

3}, Jinhua Liang^{1

2

3}, Yilin Kong^{1

2

3}, Xinyu Zhang^{1

2

3}, Jing Tang^{1

2

3}, Li Wang^{1

2

3}, Jianyong Li^{1

2

3}, Wei Xu^#^{1

2

3}, Jiazhu Wu^#^{1

2

3}

Affiliations

¹ Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People's Republic of China.
² Key Laboratory of Hematology of Nanjing Medical University, Nanjing, People's Republic of China.
³ Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a subtype of B-cell malignancy with high heterogeneity. Ferroptosis is a novel cell death induced by iron and lipid peroxidation and exhibits prognostic value in many cancers. Emerging studies on long non-coding RNAs (lncRNAs) and ferroptosis reveal the unique value in tumorigenesis. However, the prognostic value of ferroptosis-related lncRNAs (FRLs) remains unclear in CLL.

Aim: We aimed to construct a FRLs risk model to predict prognosis and improve prognostic stratification for clinical practice.

Methods: RNA-sequencing data and clinical characteristics of CLL patients were downloaded from the GEO database. Based on ferroptosis-related genes from FerrDb database, differentially expressed FRLs with prognostic significance were identified and used to generate the risk model. The capability of the risk model was assessed and evaluated. GO and KEGG analyses were performed to confirm biological roles and potential pathways.

Results: A novel ferroptosis-related lncRNAs prognostic score (FPS) model containing six FRLs (PRKCQ, TRG.AS1, LNC00467, LNC01096, PCAT6 and SBF2.AS1) was identified. Patients in the training and validation cohort were evenly divided into high- and low-risk groups. Our results indicated that patients in the high-risk group had worse survival than those in the low-risk group. Functional enrichment analyses showed that the differently expressed genes (DEGs) between the two groups were enriched in the chemokine signaling pathway, hematopoietic cell lineage, T cell differentiation, TCR pathway and NF-κB pathway. Moreover, significant differences in immune cell infiltration were also observed. Surprisingly, FPS was proved to be an independent prognostic indicator for OS.

Conclusion: We established and evaluated a novel prognostic risk model with 6 FRLs that could predict prognosis accurately and describe the distinct immune infiltration in CLL.

Keywords: chronic lymphocytic leukemia; ferroptosis; immune infiltration; long non-coding RNAs; prognosis.

Associated data

Dryad/10.5061/dryad.z612jm6fp

Grants and funding

This work was funded by National Natural Science Foundation of China (81770166, 81720108002, 81800192), Jiangsu Province’s Medical Elite Programme (ZDRCA2016022), Project of National Key Clinical Specialty, Jiangsu Provincial Special Program of Medical Science (BE2017751) and National Science and Technology Major Project (2018ZX09734007), Nature Science Foundation for Youths of Jiangsu Province (BK20171079), and Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University (PY2021026).