PMID- 36612298
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 1
DP  - 2023 Jan 1
TI  - Longitudinal Plasma Proteomics-Derived Biomarkers Predict Response to MET 
      Inhibitors for MET-Dysregulated NSCLC.
LID - 10.3390/cancers15010302 [doi]
LID - 302
AB  - MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell 
      lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to 
      the lack of powerful biomarkers. This study aims to explore the potential role of 
      plasma proteomics-derived biomarkers for patients treated with MET inhibitors 
      using mass spectrometry. We analyzed the plasma proteomics from patients with MET 
      dysregulation (including MET amplification and MET overexpression) treated with 
      MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 
      plasma samples were included. We classified patients into the PD group and non-PD 
      group based on clinical response. The baseline proteomic profiles of patients in 
      the PD group were distinct from those in the non-PD group. Through protein 
      screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) 
      could predict the efficacy of patients treated with MET inhibitors, with an area 
      under the curve (AUC) of 0.93, better than conventional fluorescence in situ 
      hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining 
      the four-protein signature with FISH or IHC test could also reach higher 
      predictive performance. Further, the combined signature could predict 
      progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also 
      validated the performance of the four-protein signature in another cohort of 
      plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma 
      protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a 
      substitutable or complementary role to conventional MET FISH or IHC tests. This 
      exploration will help select patients who may benefit from MET inhibitors.
FAU - Jie, Guang-Ling
AU  - Jie GL
AUID- ORCID: 0000-0002-4845-6280
AD  - School of Medicine, South China University of Technology, Guangzhou 510006, 
      China.
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Peng, Lun-Xi
AU  - Peng LX
AUID- ORCID: 0000-0001-6188-9737
AD  - Department of Clinical Skills Training Center, Zhujiang Hospital, Southern 
      Medical University, Guangzhou 510282, China.
FAU - Zheng, Mei-Mei
AU  - Zheng MM
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Sun, Hao
AU  - Sun H
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Wang, Song-Rong
AU  - Wang SR
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Liu, Si-Yang Maggie
AU  - Liu SM
AD  - Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou 
      510632, China.
FAU - Yin, Kai
AU  - Yin K
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Chen, Zhi-Hong
AU  - Chen ZH
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
AD  - Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, 
      Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 
      Southern Medical University, Guangzhou 510080, China.
FAU - Tian, Hong-Xia
AU  - Tian HX
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
AD  - Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, 
      Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 
      Southern Medical University, Guangzhou 510080, China.
FAU - Yang, Jin-Ji
AU  - Yang JJ
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Zhang, Xu-Chao
AU  - Zhang XC
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
AD  - Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, 
      Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 
      Southern Medical University, Guangzhou 510080, China.
FAU - Tu, Hai-Yan
AU  - Tu HY
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Zhou, Qing
AU  - Zhou Q
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
FAU - Wong, Catherine C L
AU  - Wong CCL
AD  - Clinical Research Institute, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Science & Peking Union Medical College, Beijing 100730, China.
FAU - Wu, Yi-Long
AU  - Wu YL
AUID- ORCID: 0000-0002-3611-0258
AD  - School of Medicine, South China University of Technology, Guangzhou 510006, 
      China.
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital 
      (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 
      510080, China.
LA  - eng
GR  - 2017B030314120/Guangdong Science and Technology Department/
GR  - KJ012019426/Guangdong Provincial People's Hospital/
GR  - 2022-12M-1-004/Chinese Academy of Medical Sciences &amp; Peking Union Medical 
      College/
GR  - 32150005/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230101
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9818927
OTO - NOTNLM
OT  - MET dysregulation
OT  - MET inhibitor
OT  - Non-small cell lung cancer
OT  - biomarker
OT  - proteomics
COIS- Yi-Long Wu reports consulting and advisory services and declares speaker fees for 
      Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Sanofi, Merck Sharp & Dohme, 
      and Bristol Myers Squibb. All other authors declare that they have no conflict of 
      interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/09 06:01
PMCR- 2023/01/01
CRDT- 2023/01/08 01:08
PHST- 2022/11/24 00:00 [received]
PHST- 2022/12/24 00:00 [revised]
PHST- 2022/12/29 00:00 [accepted]
PHST- 2023/01/08 01:08 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/09 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - cancers15010302 [pii]
AID - cancers-15-00302 [pii]
AID - 10.3390/cancers15010302 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Jan 1;15(1):302. doi: 10.3390/cancers15010302.