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The necroptosis signature and molecular mechanism of lung squamous cell carcinoma.
Song, Guo-Qiang; Wu, Hua-Man; Ji, Ke-Jie; He, Tian-Li; Duan, Yi-Meng; Zhang, Jia-Wen; Hu, Guo-Qiang.
Afiliación
  • Song GQ; Department of Pulmonary, Changxing County Hospital of Traditional Chinese Medicine, Huzhou, China.
  • Wu HM; Department of Pulmonary and Critical Care Medicine, Zigong First People’s Hospital, Zigong, China.
  • Ji KJ; Department of Pulmonary, Changxing County Hospital of Traditional Chinese Medicine, Huzhou, China.
  • He TL; Department of Radiotherapy, Changxing People’s Hospital, Huzhou, China.
  • Duan YM; Department of Pulmonary, Changxing County Hospital of Traditional Chinese Medicine, Huzhou, China.
  • Zhang JW; Department of Pulmonary, Changxing County Hospital of Traditional Chinese Medicine, Huzhou, China.
  • Hu GQ; Department of Pulmonary, Changxing County Hospital of Traditional Chinese Medicine, Huzhou, China.
Aging (Albany NY) ; 15(22): 12907-12926, 2023 11 15.
Article en En | MEDLINE | ID: mdl-37976123
BACKGROUND: Given the poor prognosis of lung squamous cell carcinoma (LUSC), the aim of this study was to screen for new prognostic biomarkers. METHODS: The TGCA_LUSC dataset was used as the training set, and GSE73403 was used as the validation set. The genes involved in necroptosis-related pathways were acquired from the KEGG database, and the differential genes between the LUSC and normal samples were identified using the GSEA. A necroptosis signature was constructed by survival analysis, and its correlation with patient prognosis and clinical features was evaluated. The molecular characteristics and drug response associated with the necroptosis signature were also identified. The drug candidates were then validated at the cellular level. RESULTS: The TCGA_LUSC dataset included 51 normal samples and 502 LUSC samples. The GSE73403 dataset included 69 samples. 159 genes involved in necroptosis pathways were acquired from the KEGG database, of which most showed significant differences between two groups in terms of genomic, transcriptional and methylation alterations. In particular, CHMP4C, IL1B, JAK1, PYGB and TNFRSF10B were significantly associated with the survival (p < 0.05) and were used to construct the necroptosis signature, which showed significant correlation with patient prognosis and clinical features in univariate and multivariate analyses (p < 0.05). Furthermore, CHMP4C, IL1B, JAK1 and PYGB were identified as potential targets of trametinib, selumetinib, SCH772984, PD 325901 and dasatinib. Finally, knockdown of these genes in LUSC cells increased chemosensitivity to those drugs. CONCLUSION: We identified a necroptosis signature in LUSC that can predict prognosis and identify patients who can benefit from targeted therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos