Glutathione peroxidase 4 expression predicts poor overall survival in patients with resected lung adenocarcinoma

被引:17
作者
Liu, Chao-Yu [1 ,2 ]
Liu, Chen-Chi [1 ,3 ,4 ]
Li, Anna Fen-Yau [1 ,6 ]
Hsu, Tien-Wei [4 ,5 ]
Lin, Jiun-Han [4 ,5 ]
Hung, Shih-Chieh [7 ,8 ,9 ]
Hsu, Han-Shui [4 ,5 ]
机构
[1] Natl Yang Ming Chiao Tung Univ, Fac Med, Sch Med, Taipei, Taiwan
[2] Eastern Mem Hosp, Dept Surg, Div Thorac Surg, New Taipei City, Taiwan
[3] Taipei Vet Gen Hosp, Emergency Dept, Div Traumatol, Taipei, Taiwan
[4] Taipei Vet Gen Hosp, Dept Surg, Div Thorac Surg, Taipei, Taiwan
[5] Natl Yang Ming Chiao Tung Univ Sch Med, Inst Emergency & Crit Care Med, 201,Sec 2,Shih Pai Rd, Taipei 11217, Taiwan
[6] Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan
[7] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan
[8] China Med Univ Hosp, Integrat Stem Cell Ctr, Dept Orthped, Taichung, Taiwan
[9] China Med Univ, Grad Inst New Drug Dev, BioMed Sci, Taichung, Taiwan
关键词
CANCER; OVEREXPRESSION; GPX4; EPIDEMIOLOGY; FERROPTOSIS; PHGPX;
D O I
10.1038/s41598-022-25019-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study aimed to evaluate the protein expression of glutathione peroxidase 4 (GPX4) in resected non-small cell lung cancer (NSCLC). The clinical relevance and prognostic significance of GPX4 expression were analyzed. We reviewed patients with resected NSCLCs at Taipei Veterans General Hospital between September 2002 and January 2018. Available paraffin-embedded specimens were retrieved for immunohistochemistry (IHC) staining to detect GPX4 expression. The cutoff value for defining GPX4 positivity was determined according to the percentage of tumor stained in the microscopic field. The correlation between immune expression, clinicopathologic data, overall survival (OS), and disease-free survival (DFS) were analyzed. A total of 265 NSCLC specimens were retrieved for IHC staining. GPX4 expression positive was in 192 (72.5%) according to a cutoff value of 5%. GPX4 was a significant prognostic factor for OS and DFS on multivariate analysis at both 5% and 25% cutoff values. GPX4 expression was associated with poor OS and DFS, especially in lung adenocarcinoma (p = 0.008, and 0.027, respectively). In conclusions, IHC analysis revealed that GPX4 expression was associated with poor survival outcomes in patients with resected lung adenocarcinoma. Further research is needed to understand the role of GPX4 in tumorigenesis and the underlying mechanism responsible for survival outcomes in patients with resected lung adenocarcinoma.
引用
收藏
页数:10
相关论文
共 30 条
[1]  
Aumann KD, 1997, BIOMED ENVIRON SCI, V10, P136
[2]   Lung Cancer 2020 Epidemiology, Etiology, and Prevention [J].
Bade, Brett C. ;
Dela Cruz, Charles S. .
CLINICS IN CHEST MEDICINE, 2020, 41 (01) :1-+
[3]   Glutathione peroxidases [J].
Brigelius-Flohe, Regina ;
Maiorino, Matilde .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2013, 1830 (05) :3289-3303
[4]   Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma [J].
Cejas, P. ;
Garcia-Cabezas, M. A. ;
Casado, E. ;
Belda-Iniesta, C. ;
De Castro, J. ;
Fresno, J. A. ;
Sereno, M. ;
Barriuso, J. ;
Espinosa, E. ;
Zamora, P. ;
Feliu, J. ;
Redondo, A. ;
Hardisson, D. A. ;
Renart, J. ;
Gonzalez-Baron, M. .
FREE RADICAL RESEARCH, 2007, 41 (06) :681-687
[5]   Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death [J].
Dixon, Scott J. ;
Lemberg, Kathryn M. ;
Lamprecht, Michael R. ;
Skouta, Rachid ;
Zaitsev, Eleina M. ;
Gleason, Caroline E. ;
Patel, Darpan N. ;
Bauer, Andras J. ;
Cantley, Alexandra M. ;
Yang, Wan Seok ;
Morrison, Barclay, III ;
Stockwell, Brent R. .
CELL, 2012, 149 (05) :1060-1072
[6]   Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment [J].
Duma, Narjust ;
Santana-Davila, Rafael ;
Molina, Julian R. .
MAYO CLINIC PROCEEDINGS, 2019, 94 (08) :1623-1640
[7]   GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues [J].
Guerriero, E. ;
Capone, F. ;
Accardo, M. ;
Sorice, A. ;
Costantini, M. ;
Colonna, G. ;
Castello, G. ;
Costantini, S. .
EUROPEAN JOURNAL OF HISTOCHEMISTRY, 2015, 59 (04) :283-288
[8]   CANCER The enemy of my enemy is my friend [J].
Harris, Isaac S. ;
Brugge, Joan S. .
NATURE, 2015, 527 (7577) :170-171
[9]   Blocking tumor cell eicosanoid synthesis by GPx4 impedes tumor growth and malignancy [J].
Heirman, I ;
Ginneberge, D ;
Brigelius-Flohé, B ;
Hendrickx, N ;
Agostinis, P ;
Brouckaert, P ;
Rottiers, P ;
Grooten, J .
FREE RADICAL BIOLOGY AND MEDICINE, 2006, 40 (02) :285-294
[10]   Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells [J].
Imai, H ;
Nakagawa, Y .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 34 (02) :145-169