Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas
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 gene...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023018212 |
| _version_ | 1827957493919121408 |
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| author | Feng Wang Lei Zhu |
| author_facet | Feng Wang Lei Zhu |
| author_sort | Feng Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:19:49Z |
| format | Article |
| id | doaj.art-dec8874e59e44ef4b88eded6c857ed5a |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T15:19:49Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-dec8874e59e44ef4b88eded6c857ed5a2023-04-29T14:50:23ZengElsevierHeliyon2405-84402023-04-0194e14614Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomasFeng Wang0Lei Zhu1Department of Radiotherapy, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, No. 1878, Sichuan North Road, Shanghai, 200081, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844023018212Lung squamous cell carcinomasLymph node metastasisPhenotypic plasticityPrognosisDrug responses |
| spellingShingle | Feng Wang Lei Zhu Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas Heliyon Lung squamous cell carcinomas Lymph node metastasis Phenotypic plasticity Prognosis Drug responses |
| title | Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| title_full | Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| title_fullStr | Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| title_full_unstemmed | Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| title_short | Phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| title_sort | phenotypic plasticity promotes lymph nodes metastasis and drug resistance in lung squamous cell carcinomas |
| topic | Lung squamous cell carcinomas Lymph node metastasis Phenotypic plasticity Prognosis Drug responses |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023018212 |
| work_keys_str_mv | AT fengwang phenotypicplasticitypromoteslymphnodesmetastasisanddrugresistanceinlungsquamouscellcarcinomas AT leizhu phenotypicplasticitypromoteslymphnodesmetastasisanddrugresistanceinlungsquamouscellcarcinomas |