The integrated single-cell analysis developed a lactate metabolism-driven signature to improve outcomes and immunotherapy in lung adenocarcinoma.

Background: It has been suggested that lactate metabolism (LM) is crucial for the development of cancer. Using integrated single-cell RNA sequencing (scRNA-seq) analysis, we built predictive models based on LM-related genes (LMRGs) to propose novel targets for the treatment of LUAD patients. Methods: The most significant genes for LM were identified through the use of the AUCell algorithm and correlation analysis in conjunction with scRNA-seq analysis. To build risk models with superior predictive performance, cox- and lasso-regression were utilized, and these models were validated on multiple external independent datasets. We then explored the differences in the tumor microenvironment (TME), immunotherapy, mutation landscape, and enriched pathways between different risk groups. Finally, cell experiments were conducted to verify the impact of AHSA1 in LUAD. Results: A total of 590 genes that regulate LM were identified for subsequent analysis. Using cox- and lasso-regression, we constructed a 5-gene signature that can predict the prognosis of patients with LUAD. Notably, we observed differences in TME, immune cell infiltration levels, immune checkpoint levels, and mutation landscapes between different risk groups, which could have important implications for the clinical treatment of LUAD patients. Conclusion: Based on LMRGs, we constructed a prognostic model that can predict the efficacy of immunotherapy and provide a new direction for treating LUAD.

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

Background: Lung 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. Methods: The 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. Results: A 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. Conclusion: The 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.

Cuproptosis-related lncRNA signatures: Predicting prognosis and evaluating the tumor immune microenvironment in lung adenocarcinoma.

Background: Cuproptosis, a unique kind of cell death, has implications for cancer therapy, particularly lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) have been demonstrated to influence cancer cell activity by binding to a wide variety of targets, including DNA, RNA, and proteins. Methods: Cuproptosis-related lncRNAs (CRlncRNAs) were utilized to build a risk model that classified patients into high-and low-risk groups. Based on the CRlncRNAs in the model, Consensus clustering analysis was used to classify LUAD patients into different subtypes. Next, we explored the differences in overall survival (OS), the tumor immune microenvironment (TIME), and the mutation landscape between different risk groups and molecular subtypes. Finally, the functions of LINC00592 were verified through in vitro experiments. Results: Patients in various risk categories and molecular subtypes showed statistically significant variations in terms of OS, immune cell infiltration, pathway activity, and mutation patterns. Cell experiments revealed that LINC00592 knockdown significantly reduced LUAD cell proliferation, invasion, and migration ability. Conclusion: The development of a trustworthy prediction model based on CRlncRNAs may significantly aid in the assessment of patient prognosis, molecular features, and therapeutic modalities and may eventually be used in clinical applications.