RESUMEN
BACKGROUND & AIMS: The complex tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) has hindered the development of reliable predictive biomarkers for targeted therapy and immunomodulatory strategies. A comprehensive characterization of the TME is necessary to advance precision therapeutics in PDAC. METHODS: A transcriptomic profiling platform for TME classification based on functional gene signatures was applied to 14 publicly available PDAC datasets (n = 1657) and validated in a clinically annotated independent cohort of patients with PDAC (n = 79). Four distinct subtypes were identified using unsupervised clustering and assessed to evaluate predictive and prognostic utility. RESULTS: TME classification using transcriptomic profiling identified 4 biologically distinct subtypes based on their TME immune composition: immune enriched (IE); immune enriched, fibrotic (IE/F); fibrotic (F); and immune depleted (D). The IE and IE/F subtypes demonstrated a more favorable prognosis and potential for response to immunotherapy compared with the F and D subtypes. Most lung metastases and liver metastases were subtypes IE and D, respectively, indicating the role of clonal phenotype and immune milieu in developing personalized therapeutic strategies. In addition, distinct TMEs with potential therapeutic implications were identified in treatment-naive primary tumors compared with tumors that underwent neoadjuvant therapy. CONCLUSIONS: This novel approach defines a distinct subgroup of PADC patients that may benefit from immunotherapeutic strategies based on their TME subtype and provides a framework to select patients for prospective clinical trials investigating precision immunotherapy in PDAC. Further, the predictive utility and real-world clinical applicability espoused by this transcriptomic-based TME classification approach will accelerate the advancement of precision medicine in PDAC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma Ductal Pancreático , Perfilación de la Expresión Génica , Neoplasias Pancreáticas , Medicina de Precisión , Transcriptoma , Microambiente Tumoral , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Biomarcadores de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Pronóstico , Terapia Neoadyuvante , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Valor Predictivo de las Pruebas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Bases de Datos GenéticasRESUMEN
The proposed adoption of 'scientific Globish' as a simplified language standard for scholarly communication may appeal to authors who have difficulty with English proficiency. However, Globish might not justify the hopes being pinned on it and might open the door to further deterioration of the quality of English-language scientific writing.
Asunto(s)
Autoria , Revisión de la Investigación por Pares , Consultores , HumanosRESUMEN
The benefit of publishing research in English is obvious, but so is the problem: authors with a limited knowledge of English find it difficult to compete with their proficient colleagues. In this note, we offer suggestions for improving the English of papers in the biological sciences. The suggestions aim to help authors enhance writing skills, are based on our experiences as language correctors and do not appear in major guides to scientific writing. We also argue for the need for regular publication of language tips in the pages of science journals.
