PMID- 37957027
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240206
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Linking)
VI  - 26
IP  - 1
DP  - 2024 Jan
TI  - Overexpression of VEGFA mediated by HIF-1 is associated with higher rate of 
      spread through air spaces in resected lung adenocarcinomas.
PG  - e3625
LID - 10.1002/jgm.3625 [doi]
AB  - BACKGROUND: Spread through air spaces (STAS), a newly identified pattern of 
      invasion in lung adenocarcinomas (LACs), is an unfavorable prognostic factor for 
      patients with LAC, but the molecular characteristics and mechanisms underlying 
      STAS have not been adequately explored. METHODS: In total, 650 pathologically 
      confirmed invasive LAC patients who underwent curative resection between December 
      2019 and April 2020 were reviewed. Disease-free survival (DFS) and overall 
      survival (OS) were analyzed using the log-rank test and the Cox proportional 
      hazards model. A comparative deep sequencing analysis was conducted to explore 
      the molecular characteristics underlying STAS. Vascular endothelial growth factor 
      A (VEGFA) expression was evaluated by immunoblotting and immunohistochemical 
      analysis using fresh tumor tissue and tissue microarray. RESULTS: STAS was more 
      prevalent in patients with a smoking history (p < 0.001), high pathological TNM 
      stage (p < 0.001), lymphovascular invasion (p < 0.001), visceral pleural invasion 
      (p < 0.001) and micropapillary/solid histological subtypes (p < 0.001). 
      STAS-negative patients had better DFS (p < 0.001) and OS (p = 0.003) compared to 
      STAS-positive patients with invasive LACs, especially in the lymph node-negative 
      population (p < 0.001). After RNA-sequencing analysis, hypoxia-inducible factor-1 
      (HIF-1) signaling was enriched and appeared to be strongly correlated with STAS, 
      and more STAS-positive individuals were detected in the higher VEGFA-expressing 
      group (p = 0.042). CONCLUSIONS: We demonstrated that STAS was an independent 
      prognostic marker of poor clinical outcome, especially in lymph node-negative 
      patients, and that higher VEGFA expression mediated by HIF-1 signaling was 
      associated with an increased STAS rate.
CI  - (c) 2023 John Wiley & Sons Ltd.
FAU - Guo, Liang
AU  - Guo L
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Li, Shaoling
AU  - Li S
AD  - Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Wang, Xing
AU  - Wang X
AD  - Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Zhu, Yuming
AU  - Zhu Y
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Li, Juanjuan
AU  - Li J
AUID- ORCID: 0000-0002-1431-492X
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai, China.
LA  - eng
GR  - 22120220650/Fundamental Research Funds for the Central Universities/
PT  - Journal Article
DEP - 20231113
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (VEGFA protein, human)
SB  - IM
MH  - Humans
MH  - *Lung Neoplasms/genetics/surgery/pathology
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Neoplasm Invasiveness/pathology
MH  - *Adenocarcinoma of Lung/genetics/surgery/pathology
MH  - *Adenocarcinoma/genetics/surgery/pathology
OTO - NOTNLM
OT  - VEGFA
OT  - hypoxia-inducible factor-1
OT  - lung adenocarcinomas
OT  - prognosis
OT  - spread through air spaces
EDAT- 2023/11/14 00:42
MHDA- 2024/01/30 12:42
CRDT- 2023/11/13 21:03
PHST- 2023/09/28 00:00 [revised]
PHST- 2023/08/21 00:00 [received]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2024/01/30 12:42 [medline]
PHST- 2023/11/14 00:42 [pubmed]
PHST- 2023/11/13 21:03 [entrez]
AID - 10.1002/jgm.3625 [doi]
PST - ppublish
SO  - J Gene Med. 2024 Jan;26(1):e3625. doi: 10.1002/jgm.3625. Epub 2023 Nov 13.