AIMP1 is a novel potential biomarker for LUAD and is associated with improved prognosis (preprint)

Background: Ammonia acyl tRNA synthase complex interaction of multifunctional protein 1 (AIMP1) is a specific type of cytokine, which controls angiogenesis, inflammation, and the healing of wounds. Previous studies have reported that AIMP1 exhibits anti-tumor activity. However, these studies have not determined the molecular functions of AIMP1. Moreover, scientists have not yet clearly elucidated the relationship between AIMP1 and tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) tissues. In this study, our main aim to understand how AIMP1 is related to the occurrence and development of LUAD. Moreover, we also elucidated the relationship between the expression of AIMP1 and the immune microenvironment. This new idea is the basis for providing targeted treatment to LUAD patients. Methods: To determine the expression of AIMP1 in LUAD tissues, we used the Tumor Immune Evaluation Resource (TIMER) database. To understand the relationship between the expression of AIMP1 and the survival time of LUAD patients, we constructed the Kaplan-Meier plotter with the help of R software. The LUAD data was downloaded and analyzed from the GEO database. Thus, we established a correlation between AIMP1 and various clinicopathological parameters of LUAD patients. The Western Blot technique and immunohistochemistry (IHC) tests were conducted to ascertain the expression of AIMP1 in 165 LUAD patients, which were recruited from the Affiliated Hospital of Nantong University (Nantong, Jiangsu Province, China). Thereafter, KEGG enrichment analysis and protein-protein interaction (PPI) network analysis were performed to determine the potential biological functions of AIMP1. Furthermore, the relationship between AIMP1 and tumor immune infiltration was revealed by the deconvolution algorithm of the analytical tool named CIBERSORT and the TIMER2.0 database. Results: The distribution of AIMP1 was estimated in the tumor tissues of all TCGA cancers. We found that the expression of AIMP1 was significantly enhanced in LUAD patients. However, the prognosis of LUAD patients was better when the mRNA expression of AIMP1 was upregulated. Furthermore, the protein level of AIMP1 was significantly greater in LUAD tissues (p < 0.05). By performing multivariate cox analysis, we found that AIMP1 acts as an independent prognostic factor of LUAD. Moreover, the expression of AIMP1 was found to have a correlation with tumor size and lymph node metastasis. The KEGG enrichment analysis and gene ontology (GO) database proved that AIMP1 enriched the immune-related activities of genes co-expressed with AIMP1. Cell cycle, COVID-19, and other signaling pathways were involved in this process. In addition, the expression of AIMP1 was positively correlated to the infiltration of following cell types: CD4 + T cells, activated dendritic cells, and macrophages. At the same time, they were negatively correlated to the infiltration of following cell types: B cells, regulatory T cells, and myeloid dendritic cells. Conclusions: Our findings indicate that the expression of AIMP1 was an independent prognostic factor of LUAD. Moreover, its overexpression was conducive in creating an anti-tumor immune microenvironment. However, further studies must be conducted to evaluate the potential role of AIMP1, which acts as a biomarker in eliciting an immunotherapeutic effect on LUAD patients.

SARS-COV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients

BackgroundThe outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in the lung of COVID-19 patients.MethodsWe analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated.ResultsCompared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in the lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells: interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors;on the other hand, immune-immune cells interactions appeared the strongest in mild patients.ConclusionsSARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.