Comprehensive molecular analyses of a TNF family-based signature with regard to prognosis, immune features, and biomarkers for immunotherapy in lung adenocarcinoma.
BACKGROUND
Tumour Necrosis Factor (TNF) family members play important roles in mounting anti-tumour immune responses, and clinical trials targeting these molecules are ongoing. However, the expression patterns and clinical significance of TNF members in lung adenocarcinoma (LUAD) remain unrevealed. This study aimed to explore the gene expression profiles of TNF family members in LUAD and constructed a TNF family-based prognosis signature.


METHODS
In total, 1300 LUAD cases from seven different cohorts were collected. Samples from The Cancer Genome Atlas (TCGA) were used as the training set, and the RNA data from five Gene Expression Omnibus (GEO) datasets and qPCR data from 102 samples were used for validation. The immune profiles and potential immunotherapy response prediction value of the signature were also explored.


FINDINGS
After univariate Cox proportional hazards regression and stepwise multivariable Cox analysis, a TNF family-based signature was constructed in the TCGA dataset that significantly stratified cases into high- and low-risk groups in terms of OS. This signature remained an independent prognostic factor in multivariate analyses. Moreover, the clinical significance of the signature was well validated in different clinical subgroups and independent validation cohorts. Further analysis revealed that signature high-risk patients were characterized by distinctive immune cell proportions and immune-suppressive states. Additionally, signature scores were positively related to multiple immunotherapy biomarkers.


INTERPRETATION
This was the first TNF family-based model for predicting outcomes and immune landscapes for patients with LUAD. The capability of this signature for predicting immunotherapy response needs further validation.
['Zhang|Chaoqi|C|', 'Zhang|Guochao|G|', 'Sun|Nan|N|', 'Zhang|Zhen|Z|', 'Zhang|Zhihui|Z|', 'Luo|Yuejun|Y|', 'Che|Yun|Y|', 'Xue|Qi|Q|', 'He|Jie|J|']
D000077192:Adenocarcinoma of Lung D000368:Aged D014408:Biomarkers, Tumor D019295:Computational Biology D030541:Databases, Genetic D004198:Disease Susceptibility D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D056747:Immunomodulation D008297:Male D008875:Middle Aged D005810:Multigene Family D009367:Neoplasm Staging D011379:Prognosis D015203:Reproducibility of Results D012307:Risk Factors D059467:Transcriptome D048069:Tumor Necrosis Factors
TNF Immunotherapy Immune checkpoint Lung cancer TMB