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Ferroptosis-related lncRNA signature predicts prognosis and immunotherapy efficacy in cutaneous melanoma.

作者信息

Xu Yujian, Chen Youbai, Niu Zehao, Yang Zheng, Xing Jiahua, Yin Xiangye, Guo Lingli, Zhang Qixu, Yang Yi, Han Yan

机构信息

Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing, China.

Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

出版信息

Front Surg. 2022 Jul 21;9:860806. doi: 10.3389/fsurg.2022.860806. eCollection 2022.


DOI:10.3389/fsurg.2022.860806
PMID:35937602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9354448/
Abstract

PURPOSE: Ferroptosis-related lncRNAs are promising biomarkers for predicting the prognosis of many cancers. However, a ferroptosis-related signature to predict the prognosis of cutaneous melanoma (CM) has not been identified. The purpose of this study was to construct a ferroptosis-related lncRNA signature to predict prognosis and immunotherapy efficacy in CM. METHODS: Ferroptosis-related differentially expressed genes (FDEGs) and lncRNAs (FDELs) were identified using TCGA, GTEx, and FerrDb datasets. We performed Cox and LASSO regressions to identify key FDELs, and constructed a risk score to stratify patients into high- and low-risk groups. The lncRNA signature was evaluated using the areas under the receiver operating characteristic curves (AUCs) and Kaplan-Meier analyses in the training, testing, and entire cohorts. Multivariate Cox regression analyses including the lncRNA signature and common clinicopathological characteristics were performed to identify independent predictors of overall survival (OS). A nomogram was developed for clinical use. We performed gene set enrichment analyses (GSEA) to identify significantly enriched pathways. Differences in the tumor microenvironment (TME) between the 2 groups were assessed using 7 algorithms. To predict the efficacy of immune checkpoint inhibitors (ICI), we analyzed the association between and expression and the risk score. Finally, differences in Tumor Mutational Burden (TMB) and molecular drugs Sensitivity between the 2 groups were performed. RESULTS: We identified 5 lncRNAs (AATBC, AC145423.2, LINC01871, AC125807.2, and AC245041.1) to construct the risk score. The AUC of the lncRNA signature was 0.743 in the training cohort and was validated in the testing and entire cohorts. Kaplan-Meier analyses revealed that the high-risk group had poorer prognosis. Multivariate Cox regression showed that the lncRNA signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The 1-, 3-, and 5-year survival probabilities for CM patients were 92.7%, 57.2%, and 40.2% with an AUC of 0.804, indicating a good accuracy and reliability of the nomogram. GSEA showed that the high-risk group had lower ferroptosis and immune response. TME analyses confirmed that the high-risk group had lower immune cell infiltration (e.g., CD8+ T cells, CD4+ memory-activated T cells, and M1 macrophages) and lower immune functions (e.g., immune checkpoint activation). Low-risk patients whose disease expressed or were likely to respond better to ICIs. The analysis demonstrated that the TMB had significantly difference between low- and high- risk groups. Chemotherapy drugs, such as sorafenib, Imatinib, ABT.888 (Veliparib), Docetaxel, and Paclitaxel showed Significant differences in the estimated IC50 between the two risk groups. CONCLUSION: Our novel ferroptosis-related lncRNA signature was able to accurately predict the prognosis and ICI outcomes of CM patients. These ferroptosis-related lncRNAs might be potential biomarkers and therapeutic targets for CM.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/9354448/bed7a7f768cb/fsurg-09-860806-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/9354448/334f82f9a68f/fsurg-09-860806-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/9354448/bed7a7f768cb/fsurg-09-860806-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/9354448/334f82f9a68f/fsurg-09-860806-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/9354448/bed7a7f768cb/fsurg-09-860806-g009.jpg

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Ferroptosis-related lncRNA signature predicts prognosis and immunotherapy efficacy in cutaneous melanoma.

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[5]
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[6]
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引用本文的文献

[1]
Evaluation of Ferroptosis as a Biomarker to Predict Treatment Outcomes of Cancer Immunotherapy.

Cancer Res Commun. 2025-8-1

[2]
The role of non-coding RNAs in the regulation of cell death pathways in melanoma.

Discov Oncol. 2025-6-11

[3]
Ferroptosis-related LncRNAs in diseases.

BMC Biol. 2025-6-6

[4]
Identification and Validation of a m6A-Related Long Noncoding RNA Prognostic Model in Colorectal Cancer.

J Cell Mol Med. 2025-1

[5]
LASSO regression and WGCNA-based telomerase-associated lncRNA signaling predicts clear cell renal cell carcinoma prognosis and immunotherapy response.

Aging (Albany NY). 2024-5-30

[6]
Pan-cancer analysis of super-enhancer-induced LINC00862 and validation as a SIRT1-promoting factor in cervical cancer and gastric cancer.

Transl Oncol. 2024-7

[7]
Long non-coding RNA as a potential diagnostic and prognostic biomarker in melanoma: A systematic review and meta-analysis.

J Cell Mol Med. 2024-2

[8]
Machine learning-derived identification of tumor-infiltrating immune cell-related signature for improving prognosis and immunotherapy responses in patients with skin cutaneous melanoma.

Cancer Cell Int. 2023-9-26

[9]
Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls.

Front Oncol. 2023-4-27

本文引用的文献

[1]
Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients.

Int J Gen Med. 2021-10-5

[2]
A Ferroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Cutaneous Melanoma.

Front Genet. 2021-8-10

[3]
Identification of Ferroptosis-Related Long Noncoding RNA and Construction of a Novel Prognostic Signature for Gastric Cancer.

Dis Markers. 2021

[4]
Identification and Validation of a Ferroptosis-Related Long Non-coding RNA Signature for Predicting the Outcome of Lung Adenocarcinoma.

Front Genet. 2021-7-22

[5]
Identification of a prognostic ferroptosis-related lncRNA signature in the tumor microenvironment of lung adenocarcinoma.

Cell Death Discov. 2021-7-26

[6]
Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma.

Front Mol Biosci. 2021-7-9

[7]
A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma.

Biomed Res Int. 2021

[8]
Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma.

Front Oncol. 2021-6-23

[9]
Development of a Ferroptosis-Related lncRNA Signature to Predict the Prognosis and Immune Landscape of Bladder Cancer.

Dis Markers. 2021

[10]
Long Noncoding RNA AATBC Promotes the Proliferation and Migration of Prostate Cancer Cell Through miR-1245b-5p/CASK Axis.

Cancer Manag Res. 2021-6-28

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