Development and validation of ferroptosis-related lncRNAs signature for hepatocellular carcinoma

Jiaying Liang; Yaofeng Zhi; Wenhui Deng; Weige Zhou; Xuejun Li; Zheyou Cai; Zhijian Zhu; Jinxiang Zeng; Wanlan Wu; Ying Dong; Jin Huang; Yuzhuo Zhang; Shichao Xu; Yixin Feng; Fuping Ding; Jin Zhang

doi:10.7717/peerj.11627

Development and validation of ferroptosis-related lncRNAs signature for hepatocellular carcinoma

PeerJ. 2021 Jun 11:9:e11627. doi: 10.7717/peerj.11627. eCollection 2021.

Authors

Jiaying Liang^#^{1

2}, Yaofeng Zhi^#^{1

2}, Wenhui Deng³, Weige Zhou¹, Xuejun Li¹, Zheyou Cai¹, Zhijian Zhu¹, Jinxiang Zeng¹, Wanlan Wu¹, Ying Dong¹, Jin Huang⁴, Yuzhuo Zhang^{1

2}, Shichao Xu^{1

2}, Yixin Feng^{1

2}, Fuping Ding⁵, Jin Zhang^{1

2}

Affiliations

¹ Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.
² Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China.
³ Guangzhou University of Chinese Medicine, The fourth Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China.
⁴ Guangzhou University of Chinese Medicine, Clinic of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Guangzhou University of Chinese Medicine, School of Nursing, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world. However, there is no research to establish a ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC. Therefore, this study was designed to establish a novel FRlncRNAs signature to predict the survival of patients with HCC.

Method: The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. FRlncRNAs co-expressed with ferroptosis-related genes were utilized to establish a signature. Cox regression was used to construct a novel three FRlncRNAs signature in the TCGA cohort, which was verified in the GEO validation cohort.

Results: Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature. According to the FRlncRNAs signature, the patients with HCC could be divided into low- and high-risk groups. Patients with HCC in the high-risk group displayed shorter overall survival (OS) contrasted with those in the low-risk group (P < 0.001 in TCGA cohort and P = 0.045 in GEO cohort). This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, P < 0.001), which was verified to a certain extent in the GEO cohort (univariate HR > 1, P < 0.05). Meanwhile, it was also a useful tool in predicting survival among each stratum of gender, age, grade, stage, and etiology,etc. This signature was connected with immune cell infiltration (i.e., Macrophage, Myeloid dendritic cell, and Neutrophil cell, etc.) and immune checkpoint blockade targets (PD-1, CTLA-4, and TIM-3).

Conclusion: The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.

Keywords: Ferroptosis; Gene signature; Hepatocellular carcinoma; Immunotherapy; lncRNA.

Grants and funding

This study was funded by the project of the Natural Science Foundation of Guangdong Province (2018A030313632), the Innovation and Entrepreneurship Training Program for College Students of GZUCM (S201910572049, 201910572168) and GZUCM Science Fund for Creative Research Groups (2016KYTD10) to Jin Zhang; the project of the Traditional Chinese Medicine Bureau of Guangdong Province (20211118) to Fuping Ding; and the Innovation and Entrepreneurship Training Program for College Students of GZUCM (201910572193) to Jin Huang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.