PMID- 34183593
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20230727
IS  - 1728-7731 (Electronic)
IS  - 1726-4901 (Linking)
VI  - 84
IP  - 8
DP  - 2021 Aug 1
TI  - Deep proteogenomic investigations elucidate the NRF2 antioxidant mechanism as a 
      major driving mechanism of lung adenocarcinoma in Asia.
PG  - 766-771
LID - 10.1097/JCMA.0000000000000577 [doi]
AB  - BACKGROUND: Lung adenocarcinoma is a global leading cause of death. Despite 
      modern therapeutic interventions, undesirable outcomes such as drug resistances 
      and disease recurrence still occur. Therefore, continued investigations of 
      disease driving mechanisms and counteracting strategies are urgently needed. 
      METHODS: We re-visited two deep-proteogenomic resources of lung adenocarcinoma 
      published recently. These resources were derived from patient cohorts with decent 
      sizes in Taiwan and China. The gene set enrichment analysis (GSEA) was performed. 
      A heatmap was produced by the generalized association plot (GAP). RESULTS: Among 
      189 common oncogenic pathways investigated, the nuclear factor erythroid 
      2-related factor 2 (NRF2) downstream antioxidant mechanism was uncovered for the 
      first time the leading oncogenic mechanism of lung adenocarcinoma in Taiwan. The 
      gene levels of NRF2 (also known as NFE2L2) is negatively correlated with those of 
      KEAP1 (Pearson's correlation = -0.275, p = 0.009) in patients' tumor tissues. 
      Furthermore, the protein levels of EIF2S2 and PGD are higher in patients with 
      more advanced stages in the Taiwan cohort (p = 0.001 and 0.05, respectively), and 
      are indicative of poorer progression-free survival (PFS) and overall survival 
      (OS) in the China cohort (all Cox-regression p < 0.05). On the other hand, EPHX1 
      is higher in patients with earlier stages in Taiwan (p = 0.003), and are 
      indicative of better PFS and OS in China (both Cox-regression p < 0.05). When the 
      patients were stratified using the median protein abundances for Kaplan-Meier 
      visualizations, patient strata with higher EIF2S2, PGD, and EPHX1 have 
      significantly poorer PFS (log-rank p = 0.041); poorer OS (p = 0.006), and better 
      PFS and OS (p = 0.001 and 0.030), respectively. CONCLUSION: The NRF2 downstream 
      antioxidant mechanism is one major driving mechanism of lung adenocarcinoma in 
      Asia, and represents important directions for future therapeutic interventions. 
      Major downstream proteins such as EIF2S2, PGD, and EPHX1 are indicative of cancer 
      stages and prognosis.
CI  - Copyright (c) 2021, the Chinese Medical Association.
FAU - Liang, Kung-Hao
AU  - Liang KH
AD  - Laboratory of Systems Biomedical Science, Department of Medical Research, Taipei 
      Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao 
      Tung University, Taipei, Taiwan, ROC.
AD  - Institute of Biomedical Informatics, School of Medicine, National Yang Ming Chiao 
      Tung University, Taipei, Taiwan, ROC.
FAU - Wang, Mong-Lien
AU  - Wang ML
AD  - Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao 
      Tung University, Taipei, Taiwan, ROC.
AD  - Laboratory of Molecular Oncology, Department of Medical Research, Taipei Veterans 
      General Hospital, Taipei, Taiwan, ROC.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Chin Med Assoc
JT  - Journal of the Chinese Medical Association : JCMA
JID - 101174817
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
SB  - IM
MH  - Adenocarcinoma of Lung/*genetics/*physiopathology
MH  - Aged
MH  - Algorithms
MH  - Asia
MH  - China
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - NF-E2-Related Factor 2/analysis/*genetics/*metabolism
MH  - Neoplasm Recurrence, Local/genetics
MH  - *Proteogenomics
MH  - Taiwan
COIS- Conflicts of interest: The authors declare that they have no conflicts of 
      interest related to the subject matter or materials discussed in this article.
EDAT- 2021/06/30 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/06/29 05:56
PHST- 2021/06/30 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/06/29 05:56 [entrez]
AID - 02118582-202108000-00008 [pii]
AID - 10.1097/JCMA.0000000000000577 [doi]
PST - ppublish
SO  - J Chin Med Assoc. 2021 Aug 1;84(8):766-771. doi: 10.1097/JCMA.0000000000000577.