Integrating Bulk RNA and Single-cell transcriptome to explore the role of glycan-related genes in lung adenocarcinoma.

<b>Background:</b> Despite significant advancements in the diagnosis and therapeutic management of lung adenocarcinoma (LUAD), patient outcomes continue to be suboptimal, primarily attributable to the intricate of the tumor microenvironment (TME). Recently, attention has been paid to the role of glycans and their glycosylation modifications in tumor progression. <b>Methods:</b> In the present investigation, we performed analyses to identify 13 glycan-related genes with prognostic significance in LUAD. High- and low-risk groups were distinguished by a constructed model of glycan-related genes. Single-cell analysis was performed to investigate the TME in LUAD. Drug screening analysis was utilized to predict potential candidate drugs. <b>Results:</b> High-risk patients exhibited aggressive tumor progression. Further single-cell analysis revealed that tumor cells expressing high-risk glycan-related genes displayed enhanced interactions with immune and stromal cells, suggesting that aberrant glycosylation and glycan biosynthesis may contribute to worse outcomes in LUAD by promoting immune suppression. Furthermore, based on the molecular characteristics, we identified several potential candidate drugs for personalized treatment, including docetaxel, alpelisib, and gefitinib. <b>Conclusion:</b> Our study found that glycan-related genes could alter the composition of immune cell infiltration in LUAD tumor tissues and might affect the interaction between immune cells and tumor cells through intercellular section signals, resulting in the inability of immune cells to normally initiate immune responses against tumor cells. These findings offer new biological perspectives of glycan-related genes in shaping the TME and potential targets for personalized LUAD treatment.