By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma

Abstract

BackgroundLung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs.MethodsThe most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells.ResultsA total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate.ConclusionThe eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD.

Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma

“…Sphingolipids are known to play a crucial role in tumor growth and its interactions with various pathways related to cancer (60-65). However, many genes associated with sphingolipids remain poorly understood and have not been extensively researched as potential therapeutic targets in clinical settings (66,67). We identified six genes that form a strong risk score signature.…”

Transcriptome characteristics of epithelial cells from advanced non‐small cell lung cancer were revealed by single‐cell RNA sequencing

“…6 It performs an integral function in LUAD progression with significant heterogeneity. 7 Evidence confirmed that P2RY14 may be involved in LUAD immune invasion and inhibit tumor cell immune 下Áescape within LUAD microenvironment. 8 A significant impact of JAML expression on LUAD prognosis and TME was observed, which highlights the importance of TME on LUAD patients.…”

“…Tumor microenvironment (TME) refers to the surrounding environment including tumor cells, immune cells, and stromal cells 6 . It performs an integral function in LUAD progression with significant heterogeneity 7 . Evidence confirmed that P2RY14 may be involved in LUAD immune invasion and inhibit tumor cell immune 下·escape within LUAD microenvironment 8 .…”

Integrating single-cell analysis and machine learning to create glycosylation-based gene signature for prognostic prediction of uveal melanoma

“…We employed the “seurat” and “singleR” R packages to perform quality control on scRNA-seq data ( 20 ). To ensure the data’s accuracy, we eliminated genes expressed in less than three single cells, cells with less than 200 or more than 7,000 genes, and cells with more than 10% mitochondrial genes.…”