PMID- 38322947
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 10
IP  - 3
DP  - 2024 Feb 15
TI  - Keratin gene signature expression drives epithelial-mesenchymal transition 
      through enhanced TGF-beta signaling pathway activation and correlates with adverse 
      prognosis in lung adenocarcinoma.
PG  - e24549
LID - 10.1016/j.heliyon.2024.e24549 [doi]
LID - e24549
AB  - BACKGROUND: Lung adenocarcinoma (LUAD) stands as the foremost histological 
      subtype of non-small-cell lung cancer, accounting for approximately 40% of all 
      lung cancer diagnoses. However, there remains a critical unmet need to enhance 
      the prediction of clinical outcomes and therapy responses in LUAD patients. 
      Keratins (KRTs), serving as the structural components of the intermediate 
      filament cytoskeleton in epithelial cells, play a crucial role in the advancement 
      of tumor progression. This study investigated the prognostic significance of the 
      KRT family gene and developed a KRT gene signature (KGS) for prognostic 
      assessment and treatment guidance in LUAD. METHODS: Transcriptome profiles and 
      associated clinical details of LUAD patients were meticulously gathered from The 
      Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The KGS 
      score was developed based on the expression of five prognostic KRT genes (KRT7, 
      KRT8, KRT17, KRT18, and KRT80), and the upper quartile of the KGS score was 
      chosen as the cutoff. The Kaplan-Meier method was evaluated to compare survival 
      outcomes between KGS-high and KGS-low groups. The underlying mechanism was 
      further investigated by GSEA, GSVA, and other bioinformatic algorithms. RESULTS: 
      High expression of the KGS signature exhibited a robust association with poorer 
      overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35-2.42, 
      P = 0.00011). The association was further corroborated in three external GEO 
      cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7-6.47, P = 0.00017), GSE72094 
      (HR: 1.95; 95% CI: 1.34-2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 
      1.74-5.84, P < 0.0001). Interestingly, KGS-high tumors revealed enrichments in 
      TGF-beta and WNT-beta catenin signaling pathways, exhibited heightened activation of 
      the epithelial-mesenchymal transition (EMT) pathway and proved intensified tumor 
      stemness compared to their KGS-low counterparts. Additionally, KGS-high tumor 
      cells exhibited increased sensitivity to several targeted agents, including 
      gefitinib, erlotinib, lapatinib, and trametinib, in comparison to KGS-low cells. 
      CONCLUSION: This study developed a KGS score that independently predicts the 
      prognosis in LUAD. High expression of KGS score, accompanied by upregulation of 
      TGF-beta and WNT-beta catenin signaling pathways, confers more aggressive EMT and tumor 
      progression.
CI  - (c) 2024 Published by Elsevier Ltd.
FAU - Li, Gang
AU  - Li G
AD  - Department of Thoracic Surgery, Sichuan Academy of Medical Sciences and Sichuan 
      People's Hospital, University of Electronic Science and Technology of China, 
      Chengdu, 610072, China.
FAU - Guo, Jinbao
AU  - Guo J
AD  - Department of Cardiothoracic Surgery, First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, 400016, China.
FAU - Mou, Yunfei
AU  - Mou Y
AD  - Department of Thoracic Surgery, Chengdu Third People's Hospital, Chengdu, 610082, 
      China.
FAU - Luo, Qingsong
AU  - Luo Q
AD  - Department of Thoracic Surgery, Sichuan Academy of Medical Sciences and Sichuan 
      People's Hospital, University of Electronic Science and Technology of China, 
      Chengdu, 610072, China.
FAU - Wang, Xuehai
AU  - Wang X
AD  - Department of Thoracic Surgery, Sichuan Academy of Medical Sciences and Sichuan 
      People's Hospital, University of Electronic Science and Technology of China, 
      Chengdu, 610072, China.
FAU - Xue, Wei
AU  - Xue W
AD  - Burning Rock Biotech, Guangzhou, 510300, China.
FAU - Hou, Ting
AU  - Hou T
AD  - Burning Rock Biotech, Guangzhou, 510300, China.
FAU - Zeng, Tianyang
AU  - Zeng T
AD  - Department of Cardiothoracic Surgery, First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, 400016, China.
FAU - Yang, Yi
AU  - Yang Y
AD  - Department of Thoracic Surgery, Chengdu Third People's Hospital, Chengdu, 610082, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20240117
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10844058
OTO - NOTNLM
OT  - Drug sensitivity
OT  - EMT
OT  - Keratins
OT  - Lung adenocarcinoma (LUAD)
OT  - Prognosis
OT  - TGF-beta signaling
OT  - WNT-beta catenin signaling
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/02/07 06:42
MHDA- 2024/02/07 06:43
PMCR- 2024/01/17
CRDT- 2024/02/07 04:09
PHST- 2023/02/05 00:00 [received]
PHST- 2023/12/13 00:00 [revised]
PHST- 2024/01/10 00:00 [accepted]
PHST- 2024/02/07 06:43 [medline]
PHST- 2024/02/07 06:42 [pubmed]
PHST- 2024/02/07 04:09 [entrez]
PHST- 2024/01/17 00:00 [pmc-release]
AID - S2405-8440(24)00580-2 [pii]
AID - e24549 [pii]
AID - 10.1016/j.heliyon.2024.e24549 [doi]
PST - epublish
SO  - Heliyon. 2024 Jan 17;10(3):e24549. doi: 10.1016/j.heliyon.2024.e24549. 
      eCollection 2024 Feb 15.