PMID- 37025908
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230411
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 9
IP  - 4
DP  - 2023 Apr
TI  - Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung 
      squamous cell carcinomas.
PG  - e14614
LID - 10.1016/j.heliyon.2023.e14614 [doi]
LID - e14614
AB  - BACKGROUND: Phenotypic plasticity (PP) is a major promoter of tumor metastasis 
      and drug resistance. Nevertheless, the molecular features and clinical 
      significance of phenotypic plasticity in lung squamous cell carcinomas (LSCC) 
      remained largely unexplored. METHODS: Phenotypic plasticity-related genes (PPRG) 
      and clinical information of LSCC were downloaded from the cancer genome atlas 
      (TCGA). The expression profiles of PPRG were compared between patients with and 
      without lymph node metastasis. The prognostic signature was constructed, and 
      survival analysis was performed based on phenotypic plasticity. Immunotherapy 
      responses, chemotherapeutic drugs and targeted drug responses were investigated. 
      In addition, the results were verified in an external cohort. RESULTS: Patients 
      with and without lymph node metastasis exhibited significantly different genomic 
      characteristics of phenotypic plasticity. Enrichment analysis showed that PP was 
      strongly associated with cell responses and cell contraction. Survival analysis 
      demonstrated that PPRG could serve as independent prognostic factor for overall 
      survival. The phenotypic plasticity-related signature successfully divided 
      patients into high- and low-PP score groups. Patients with low-PP scores were 
      more sensitive to PD-L1, Cisplatin, Gefitinib, Obatoclax. Mesylate, Paclitaxel, 
      Sorafenib and Vinorelbine (all p < 0.05). While, patients with low-PP scores were 
      more sensitive to Axitinib and Camptothecin (all p < 0.05). Consistent with the 
      results from TCGA, the external cohort validated the above findings. CONCLUSIONS: 
      Our study revealed that phenotypic plasticity may be involved in the lymph node 
      metastasis in LSCC through regulating cell responses and cell contraction. 
      Evaluation of phenotypic plasticity will assist clinicians in making treatment 
      strategies.
CI  - (c)2023PublishedbyElsevierLtd.
FAU - Wang, Feng
AU  - Wang F
AD  - Department of Radiotherapy, Shanghai Fourth People's Hospital, School of 
      Medicine, Tongji University, No. 1878, Sichuan North Road, Shanghai, 200081, 
      China.
FAU - Zhu, Lei
AU  - Zhu L
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, 
      Tongji University, 507 Zhengmin Road, Shanghai, 200433, China.
LA  - eng
PT  - Journal Article
DEP - 20230317
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10070384
OTO - NOTNLM
OT  - Drug responses
OT  - Lung squamous cell carcinomas
OT  - Lymph node metastasis
OT  - Phenotypic plasticity
OT  - Prognosis
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/08 06:00
MHDA- 2023/04/08 06:01
PMCR- 2023/03/17
CRDT- 2023/04/07 02:35
PHST- 2022/11/18 00:00 [received]
PHST- 2023/03/11 00:00 [revised]
PHST- 2023/03/13 00:00 [accepted]
PHST- 2023/04/08 06:01 [medline]
PHST- 2023/04/07 02:35 [entrez]
PHST- 2023/04/08 06:00 [pubmed]
PHST- 2023/03/17 00:00 [pmc-release]
AID - S2405-8440(23)01821-2 [pii]
AID - e14614 [pii]
AID - 10.1016/j.heliyon.2023.e14614 [doi]
PST - epublish
SO  - Heliyon. 2023 Mar 17;9(4):e14614. doi: 10.1016/j.heliyon.2023.e14614. eCollection 
      2023 Apr.