Construction and validation of a T cell proliferation regulator-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma

Abstract

BackgroundAs the main executor of immunotherapy, T cells significantly affect the efficacy of immunotherapy. However, the contribution of the T cell proliferation regulator to the prognosis of lung adenocarcinoma (LUAD) and immunotherapy is still unclear.MethodsBased on T cell proliferation regulators, LUAD samples from The Cancer Genome Atlas (TCGA) were divided into two different clusters by consensus clustering. Subsequently, the T cell proliferation regulator (TPR) signature was constructed according to the prognostic T cell proliferation regulators. Combined with clinical information, a nomogram for clinical practice was constructed. The predictive ability of the signature was verified by the additional Gene Expression Omnibus (GEO) dataset. We also analyzed the differences of tumor microenvironment (TME) in different subgroups and predicted the response to immunotherapy according to the TIDE algorithm. Finally, we further explored the role of ADA (Adenosine deaminase) in the lung adenocarcinoma cell lines through the knockdown of ADA. ResultsAccording to the consensus clustering, there were differences in survival and tumor microenvironment between two different molecular subtypes. T cell proliferation regulator-related signature could accurately predict the prognosis of LUAD. The low-risk group had a higher level of immune infiltration and more abundant immune-related pathways, and its response to immunotherapy was significantly better than the high-risk group (Chi-square test, p<0.0001). The knockdown of ADA inhibited proliferation, migration, and invasion in lung adenocarcinoma cell lines.ConclusionT cell proliferation regulators were closely related to the prognosis and tumor microenvironment of LUAD patients. And the signature could well predict the prognosis of LUAD patients and their response to immunotherapy. ADA may become a new target for the treatment of LUAD.

Identification of Immunogenic cell death-Related Subgroups and Prognosis Model in lung adenocarcinoma

“…Adenosine deaminase (ADA) regulates intracellular adenosine levels, and increased ADA activity is associated with the disease stages of gastric, bladder, breast, colorectal and renal cell carcinoma (Zhulai, et al 2022). Relevant literature has shown that ADA knockout can affect the proliferation, invasion and migration of LUAD, but it has not been veri ed in vivo (Chang, et al 2023). In our study, ADA, as a risk factor for lung adenocarcinoma, was associated with poor clinical outcomes, suggesting that targeting ADA may be a new target for the treatment of LUAD, but its mechanism needs to be further validated and further studied.…”