RETRACTED: Development of the ARDS‐derived gene panel for lung adenocarcinoma prognosis stratification and experiment validation of CCL20 expression

Abstract

Acute respiratory distress syndrome (ARDS) is a life‐threatening condition characterized by lung inflammation and high mortality rates. Lung cancer, specifically lung adenocarcinoma (LUAD), is a major cause of cancer‐related deaths worldwide. Patients with LUAD, particularly those undergoing chemotherapy, are more likely to develop ARDS. ARDS inflicts major malfunctioning in the immune system. We suspected a certain shared pathogenic mechanism between these diseases. This study analyzed 503 LUAD patients from the TCGA‐LUAD cohort as the training set, 85 LUAD cases from the GSE30219 cohort as the validation set, and 24 RNA‐seq samples from ARDS mice model and control groups in the GSE2411 cohort. The differentially expressed genes (DEGs) of ARDS were analyzed using the limma package and screened by Cox and Lasso analysis. ssGSEA and xCell algorithms were utilized for immune landscaping. RT‐qPCR analysis was used to determine the mRNA levels of key genes in both the LPS‐induced ARDS model and human LUAD cell lines. We identified DEGs between ARDS and control groups, which were highly associated with cytokine production and leukocyte migration. A prognosis model for LUAD patients was developed based on the expressions of the key genes in the ARDS‐derived DEGs, including FMO3, IL1R2, CCL20, CFTR, and GADD45G. A satisfactory efficacy was observed in both the training and validation cohorts. The model demonstrated increased effectiveness in predicting the intratumor immune profile and mutation status of LUAD. Moreover, we utilized LPS to induce the ARDS model, which resulted in elevated expressions of IL1R2 and CCL20. Additionally, CCL20 was upregulated in cancerous LUAD cell lines. We developed an ARDS‐based model for stratifying LUAD prognosis. CCL20 was found to be elevated in both the ARDS model and LUAD, suggesting a shared underlying mechanism of these two diseases.