A ferroptosis-related gene signature predicts overall survival in patients with lung adenocarcinoma

被引:36
作者
Gao, Xinliang [1 ]
Tang, Mingbo [1 ]
Tian, Suyan [2 ]
Li, Jialin [1 ]
Liu, Wei [1 ]
机构
[1] First Hosp Jilin Univ, Dept Thorac Surg, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China
[2] First Hosp Jilin Univ, Div Clin Res, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China
关键词
bioinformatics; ferroptosis; lung adenocarcinoma; signature; survival; TCGA; EXPRESSION; SORAFENIB; PROTECTS;
D O I
10.2217/fon-2020-1113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aims: To elucidate the association between ferroptosis-related genes and prognosis in patients with lung adenocarcinoma (LUAD). Materials & methods: A ferroptosis-related gene signature was made by lasso regression analysis through the LUAD datasets of the Cancer Genome Atlas. The prognostic value of the multigene signature was externally validated in the GSE72094 dataset from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were used to explore underlying mechanisms. Results and conclusion: We established a novel ferroptosis-related gene signature for overall survival in LUAD that was predictive in both the training and validation cohorts. Immune-related pathways were significantly enriched, and immune status differed between the high- and low-risk groups. Targeting ferroptosis is a potential therapeutic option in LUAD. These results still need to be confirmed by more studies. Lay abstract: Lung adenocarcinoma (LUAD) is a common type of lung cancer, a major contributor to cancer-related death in men and women worldwide. Ferroptosis is a form of regulated cell death that is dependent on iron. The relationship between ferroptosis-related gene expression and survival in patients with LUAD remains to be elucidated. In this article, the public datasets the Cancer Genome Atlas and the Gene Expression Omnibus were used to create a model with 12 ferroptosis genes to separate LUAD patients into high- and low-risk groups. The low-risk group had better survival than the high-risk group. We also found that the immune status was different in high-risk and low-risk patients. In conclusion, our study established a novel ferroptosis-related gene signature for survival in LUAD. The underlying mechanisms involve tumor immunity.
引用
收藏
页码:1533 / 1544
页数:12
相关论文
共 34 条
[1]   Interferon γ and Its Important Roles in Promoting and Inhibiting Spontaneous and Therapeutic Cancer Immunity [J].
Alspach, Elise ;
Lussier, Danielle M. ;
Schreiber, Robert D. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2019, 11 (03)
[2]   NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis [J].
Alvarez, Samantha W. ;
Sviderskiy, Vladislav O. ;
Terzi, Erdem M. ;
Papagiannakopoulos, Thales ;
Moreira, Andre L. ;
Adams, Sylvia ;
Sabatini, David M. ;
Birsoy, Kivanc ;
Possemato, Richard .
NATURE, 2017, 551 (7682) :639-+
[3]   The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis [J].
Bersuker, Kirill ;
Hendricks, Joseph M. ;
Li, Zhipeng ;
Magtanong, Leslie ;
Ford, Breanna ;
Tang, Peter H. ;
Roberts, Melissa A. ;
Tong, Bingqi ;
Maimone, Thomas J. ;
Zoncu, Roberto ;
Bassik, Michael C. ;
Nomura, Daniel K. ;
Dixon, Scott J. ;
Olzmann, James A. .
NATURE, 2019, 575 (7784) :688-+
[4]   Down-expression of miR-152 lead to impaired anti-tumor effect of NK via upregulation of HLA-G [J].
Bian, Xiaokun ;
Si, Yuanquan ;
Zhang, Min ;
Wei, Ran ;
Yang, Xiaomin ;
Ren, Hao ;
Zheng, Guixi ;
Wang, Chuanxin ;
Zhang, Yi .
TUMOR BIOLOGY, 2016, 37 (03) :3749-3756
[5]   The International Epidemiology of Lung Cancer: Latest Trends, Disparities, and Tumor Characteristics [J].
Cheng, Ting-Yuan David ;
Cramb, Susanna M. ;
Baade, Peter D. ;
Youlden, Danny R. ;
Nwogu, Chukwumere ;
Reid, Mary E. .
JOURNAL OF THORACIC ONCOLOGY, 2016, 11 (10) :1653-1671
[6]   Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis [J].
Dixon, Scott J. ;
Patel, Darpan ;
Welsch, Matthew ;
Skouta, Rachid ;
Lee, Eric ;
Hayano, Miki ;
Thomas, Ajit G. ;
Gleason, Caroline ;
Tatonetti, Nicholas ;
Slusher, Barbara S. ;
Stockwell, Brent R. .
ELIFE, 2014, 3
[7]   FSP1 is a glutathione-independent ferroptosis suppressor [J].
Doll, Sebastian ;
Freitas, Florencio Porto ;
Shah, Ron ;
Aldrovandi, Maceler ;
da Silva, Milene Costa ;
Ingold, Irina ;
Grocin, Andrea Goya ;
da Silva, Thamara Nishida Xavier ;
Panzilius, Elena ;
Scheel, Christina H. ;
Mourao, Andre ;
Buday, Katalin ;
Sato, Mami ;
Wanninger, Jonas ;
Vignane, Thibaut ;
Mohana, Vaishnavi ;
Rehberg, Markus ;
Flatley, Andrew ;
Schepers, Aloys ;
Kurz, Andreas ;
White, Daniel ;
Sauer, Markus ;
Sattler, Michael ;
Tate, Edward William ;
Schmitz, Werner ;
Schulze, Almut ;
O'Donnell, Valerie ;
Proneth, Bettina ;
Popowicz, Grzegorz M. ;
Pratt, Derek A. ;
Angeli, Jose Pedro Friedmann ;
Conrad, Marcus .
NATURE, 2019, 575 (7784) :693-+
[8]  
Ferrer Miriam, 2005, Clin Lung Cancer, V6, P250, DOI 10.3816/CLC.2005.n.005
[9]   New biological perspectives for the improvement of the efficacy of sorafenib in hepatocellular carcinoma [J].
Galmiche, Antoine ;
Chauffert, Bruno ;
Barbare, Jean-Claude .
CANCER LETTERS, 2014, 346 (02) :159-162
[10]   Targeting Ferroptosis to Iron Out Cancer [J].
Hassannia, Behrouz ;
Vandenabeele, Peter ;
Vanden Berghe, Tom .
CANCER CELL, 2019, 35 (06) :830-849