Abstract
BACKGROUND: The tumor necrosis factor (TNF) family plays a role in modulating cellular functions that regulate cellular differentiation, survival, apoptosis, and especially cellular immune functions. The TNF family members also play important roles in oncogenesis and progression. However, the potential role of the TNF family members in lung adenocarcinoma (LUAD) is yet to be explored. METHODS: The expression of TNF-related genes (TNFRGs) in 1,093 LUAD samples was investigated using The Cancer Genome Atlas and Gene Expression Omnibus datasets. The characteristic patterns of TNFRGs in LUAD were systematically probed and three distinct molecular subtypes were identified. Furthermore, a correlation was found between the different subtypes and their clinical characteristics. A TNF scoring system was created to predict overall survival (OS) and therapeutic responses in patients with LUAD. Subsequently, the predictive accuracy of the score was verified and a nomogram was used to optimize the clinical applicability range of the TNF score. RESULTS: A high TNF score, involving the immune and stromal scores, indicated negative odds of OS. Moreover, the TNF score was associated with immune checkpoints and chemotherapeutic drug sensitivity. Collectively, our comprehensive TNFRGs analysis of patients with LUAD revealed that TNF could be involved in forming the diverse and complex tumor microenvironment, its clinicopathological features, and its prognosis. CONCLUSIONS: A TNF-related prognostic model was constructed, and a TNF score was developed. These findings are expected to improve our knowledge regarding the function of TNFRGs in LUAD, pave a new path for assessing the disease prognosis, and assist in developing personalized therapeutic strategies for patients with LUAD.