Absent in melanoma 2 (AIM2) positive profile identifies a poor prognosis of lung adenocarcinoma patients.
2023
Colarusso, C | Terlizzi, M | Falanga, A | Stathopoulos, G | De Lucia, L | Hansbro, PM | Pinto, A | Sorrentino, R
The absent in melanoma 2 (AIM2) inflammasome has been demonstrated as involved in tumor growth. In this study we used human samples of lung adenocarcinoma (LUAD) patients, taking advantage of a mouse model of smoking cessation. Human samples were stratified according to the smoking status, high-risk factor for this type of tumor. Both public transcriptomic and human samples obtained by a clinical trial proved that AIM2 was upregulated either in terms of mRNA or protein, respectively, in the tumor mass according to the TNM stage, but it did not relate to the smoking status, age and sex. The upregulation of AIM2 was correlated to an immunosuppressive environment according to resting/non-active dendritic cells (DCs) and T regulatory cells, as demonstrated in both human samples and by means of an experimental model of smoking mice. Computational analysis showed that AIM2 upregulation was correlated to both an inflammasome profile, responsible for the poor prognosis of non-smoker and smoker LUAD patients, and to a non-inflammasome profile for former smoker. In conclusion, our study demonstrated that AIM2 is involved in lung carcinogenesis either in a canonical and non-canonical manner due to an immunosuppressive microenvironment associated to a dismal prognosis of LUAD patients.
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Эту запись предоставил University of Technology Sydney