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Prognostic Signature Constructed of Seven Ferroptosis-Related lncRNAs Predicts the Prognosis of HBV-Related HCC

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Abstract

Background

Ferroptosis and lncRNAs both play crucial roles in cancers. But the roles of ferroptosis-related lncRNAs (FRLncs) in HBV-related HCC (HBV-HCC) remain ambiguous.

Methods

The gene expression profile and clinical data were originated from the Cancer Genome Atlas (TCGA) database. The risk signature was constructed by FRLncs based on the Cox regression analysis. The survival curve, Cox regression analysis, and time-dependent receiver operating characteristic (ROC) curve were adopted to verify the independence and reliability of the signature. A nomogram was established. Immune-infiltrating cells, immune functions, and checkpoints were analyzed.

Results

A risk signature composed of 7 FRLncs (LINC00942, AC131009.1, POLH-AS1, AC090772.3, MKLN1-AS, AC009403.1, AL031985.3) was constructed and divided HBV-HCC patients into high- and low-risk groups. Patients in the high-risk group showed a poor prognosis. The area under curves (AUC) of the signature for 1-, 3-, and 5-year was satisfactory. A nomogram composed of gender, stage, age, grade, and risk signature was established. The risk signature and nomogram displayed appreciable independence and reliability in HBV-HCC patients. The T-cell CD8 + , monocyte, and macrophage M1 were expressed differently significantly in HCC patients, while macrophage M2 showed an obvious difference in the HBV-HCC patients between the different risk groups. PDCD1 and CTL4 were expressed higher in the high-risk group of HCC patients.

Conclusion

A 7-lncRNA signature was identified as a potential prognostic predictor for HBV-HCC patients. Immune therapy may be a promising strategy for HCC patients, especially HBV-HCC patients.

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Data Availability

The RNA sequencing data with clinical information were acquired from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/). The ferroptosis-related genes were acquired from the FerrDb V2 (http://www.zhounan.org/ferrdb/current/). The Infiltration Estimation for all TCGA tumors was downloaded from TIMER2.0 (http://timer.cistrome.org/). The authors confirm that the data supporting the findings of this study are available within the article.

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Funding

This work was supported by the Natural Foundation of Shandong Province (No. ZR2020QH035 and No. ZR2021QH195) and the Medical Health Science and Technology Development Plan Project of Shandong Province (No. 202103030765).

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 **g 5 Rd, **an, Shandong, 250021, China

    Wenwen Wang, Lifen Wang, Tong Mu, **hua Hu & Hua Feng

  2. Department of Emergency Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, **an, Shandong, China

    Chunxia Song

Authors
  1. Wenwen Wang
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  2. Lifen Wang
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  4. Tong Mu
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  6. Hua Feng
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Wenwen Wang, Lifen Wang, Tong mu, Chunxia Song and **hua Hu. The first draft of the manuscript was written by Wenwen Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hua Feng.

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Key findings

1. Prognostic signature constructed of seven ferroptosis-related lncRNAs displayed appreciable independence and reliability both in HBV and HBV-HCC patients.

2. The risk signature stratified patients into high- and low-risk groups which could help guide the personalized therapy in the future.

What is known and what is new?

• Both the lncRNAs and ferroptosis play important roles in the multiple cancers.

• Ferroptosis-related lncRNAs composed a risk signature which was considered to be an independent prognostic factor for HBV-HCC patients and had good predictive accuracy for long-term survival probability.

What is the implication, and what should change now?

• Ferroptosis combined with immune therapy may be a promising strategy for all HCC patients, especially HBV-HCC patients. Further, in vitro and in vivo studies were needed to verify.

• the relevant mechanisms.

Supplementary Information

Below is the link to the electronic supplementary material.

12029_2023_977_MOESM1_ESM.zip

Supplemental Table 1: 484 FRGs downloaded from the FerrDb V2 database. Supplemental Table 2: 1317 lncRNAs were identified as FRLncs through the co-expression analysis. Supplemental Table 3: 141 differently expressed ferroptosis related genes were recognized based on the differential expression analysis. Supplementary Table 4: 784 differentially expressed ferroptosis related lncRNAs were discerned according to the differential expression analysis. Supplementary Table 5: The median value of each FRLncs calculated by the SPSS software. Supplementary Table 6: The risk signature constructed based on the LASSO regression. Supplementary Figure 1: (A) 12 FRLncs were screened in the LASSO regression model. (B) regression coefficient profiles of 12 FRLncs in the LASSO model. (C) The ROC curve of the risk signature constructed based on the LASSO regression. (ZIP 506 KB)

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Wang, W., Wang, L., Song, C. et al. Prognostic Signature Constructed of Seven Ferroptosis-Related lncRNAs Predicts the Prognosis of HBV-Related HCC. J Gastrointest Canc 55, 444–456 (2024). https://doi.org/10.1007/s12029-023-00977-6

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