Lower Expression of TWEAK is Associated with Poor Survival and Dysregulate TIICs in Lung Adenocarcinoma.
Dis Markers
; 2022: 8661423, 2022.
Article
en En
| MEDLINE
| ID: mdl-35707713
ABSTRACT
Background:
Lung cancer remains the leading cause of cancer death worldwide, and the most subtype is lung adenocarcinoma (LUAD). Tumor-infiltrating immune cells (TIICs) greatly impact the prognosis of LUAD. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), signal via its receptor fibroblast growth factor-inducible 14 (Fn14), dysregulates immune cell recruitment within tumor environment, thus promoting the progression of autoimmune diseases and cancer. We aimed to explore its role in LUAD.Methods:
The expression level of TWEAK was explored in Tumor Immune Estimation Resource 2.0 (TIMER2.0) and Oncomine databases. The Tumor Immune Dysfunction and Exclusion (TIDE) and Lung Cancer Explorer (LCE) databases were applied to evaluate the survival in correlation to TWEAK expression. TIICs were assessed with TIMER2.0 and TIDE datasets. The expression of TWEAK protein was detected in LUAD cell lines and also in tissue samples from LUAD patients via western blotting or combination with immunochemistry.Results:
Our results showed that TWEAK was downregulated in LUAD tumors compared to normal tissues in TIMER2.0, Oncomine, cell lines, and clinical specimens. Poor survival was uncovered in lower TWEAK expression of LUAD patients in LCE (meta - HR = 0.84 [95% CI, 0.76-0.92]) and TCGA (Continuous Z = -1.97, p = 0.0486) and GSE13213@PRECOG (Continuous Z = -4.25, p = 2.12e - 5) in TIDE. Multiple tumor-infiltrating immune cells (TIICs) were found closely correlated with TWEAK expression in LUAD, especially hematopoietic stem cell (Rho = 0.505, p = 2.78e - 33), common lymphoid progenitor (Rho = -0.504, p = 3.79e - 33), and myeloid-derived suppressor cells (MDSCs) (Rho = -0.615, p = 1.36e - 52).Conclusion:
Lower level of TWEAK was linked with poor survival and aberrant recruitment and phenotype of TIICs in LUAD, which might motivate immune escape and weaken the effects of immunotherapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos Infiltrantes de Tumor
/
Citocina TWEAK
/
Adenocarcinoma del Pulmón
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Dis Markers
Asunto de la revista:
BIOQUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China