Ceramide Pathway Regulators Predict Clinical Prognostic Risk and Affect the Tumor Immune Microenvironment in Lung Adenocarcinoma

Abstract

The ceramide pathway is strongly associated with the regulation of tumor proliferation, differentiation, senescence, and apoptosis. This study aimed to explore the gene signatures, prognostic value, and immune-related effects of ceramide-regulated genes in lung adenocarcinoma (LUAD). Methods: Public datasets of LUAD from The Cancer Genome Atlas and Gene Expression Omnibus were selected. Consensus clustering was adopted to classify LUAD patients, and a least absolute shrinkage and selection operator (LASSO) regression model was employed to develop a prognostic risk signature. CIBERSORT algorithm was used to estimate the association between the risk signature and the tumor immune microenvironment. Results: Most of the 22 ceramide-regulated genes were differentially expressed between LUAD and normal samples. LUAD patients were classified into two subgroups (cluster 1 and 2) and cluster 2 was associated with a poor prognosis. Furthermore, a prognostic risk signature was developed based on the three ceramide-regulated genes, Cytochrome C (CYCS), V-rel reticuloendotheliosis viral oncogene homolog A (RELA) and Fas-associated via death domain (FADD). LUAD patients with low-and high-risk scores differed concerning the subtypes of tumor−infiltrating immune cells. A moderate to weak correlation was observed between the risk score and tumor−infiltrating immune cells. Conclusions: Ceramide-regulated genes could predict clinical prognostic risk and affect the tumor immune microenvironment in LUAD.

A more novel and powerful prognostic gene signature of lung adenocarcinoma determined from the immune cell infiltration landscape

“…Whether the LUAD prognostic model we established in this study has an advantage, we also answer in this paper. By comparison, the prognostic power of our model was better than the eight studies ( 51 – 58 ) from the most recent year.…”

A novel defined pyroptosis-related gene signature predicts prognosis and correlates with the tumour immune microenvironment in lung adenocarcinoma

“…However, the mechanisms by which BAK1 mediates pyroptosis and leads to LUAD remain elusive. CYCS , as a mitochondrial protein that participates in the regulation of cell death, was reported to be an oncogene in LUAD 35 . Previous research has demonstrated that serum CYCS levels are correlated with disease progression and a poor prognosis in NSCLC 36 , which is consistent with our current results.…”

A BIRC5High COD1Low Cancer Tissue Phenotype Indicates Poorer Prognosis of Metastatic Breast Cancer Patients

“…Next, we used UALCAN to analyze the relationship between mRNA expression of BIRC5 and CDO1 and clinical staging of AJCC-TNM in breast cancer patients. 22 Furthermore, the information on tumor immune estimation was obtained from the TIMER database ( https://cistrome.shinyapps.io/timer/ ) 23 and followed by some relevant literature retrieval. 24 We analyzed the correlation of BIRC5 or CDO1 mRNA levels with infiltrated immune cells and immune markers of various immune cells in breast cancer tissue.…”