Integrated multi-omics profiling to dissect the development of second primary lung cancer in laryngeal cancer

Abstract

Abstract Objective: Laryngeal cancer is a prevalent form of malignant tumor that often leads to death as a result of the development of a second primary lung cancer. Previous studies have not examined the relationship between these two types of cancer. Therefore, our objective was to investigate the causal mechanism behind the development of second primary lung cancer in individuals with laryngeal cancer using multi-omics approaches. Methods: The datasets for laryngeal cancer (GSE51985) and lung cancer (GSE102287) were obtained from the GEO. Different genes were performed using the 'limma' package, followed by construction of the PPI network. Enrichment analysis was conducted using the DAVID, and the NetworkAnalst was utilized to establish transcription factor-miRNA and gene interactions. Receiver operating characteristic curve analysis (ROC analysis) was performed using SPSS to plot the area under the curve (AUC). Bacterial lipopolysaccharide-related genes were obtained from the CTD, and relevant genes were screened for metabolic analysis. Additionally, the GSE150321 and GSE127471 datasets from the GEO were used for single-cell RNA analysis and metabolic analysis. Finally, the 'Cibersort' package was employed to assess the infiltration status of 22 different immune cells. Results: The study found that laryngeal and lung cancers showed higher expression of UBE2C, POLQ, RAD51, and HOXB7, while lower expression was observed for EDNRB, GPD1L, F10, SORBS2, and CXCL12. These genes were mainly enriched in Pathways in cancer, which are closely associated with the cell cycle. Additionally, the study identified 120 TFs and 246 miRNAs that coordinated these shared genes. These genes have potential as diagnostic markers for laryngeal and lung cancers. Metabolic analysis of CXCL12 revealed involvement in inositol phosphate metabolism. Furthermore, single-cell RNA sequencing analysis demonstrated that intermediate monocytes in lung cancer exhibited greater activity and expression of components compared to other cells. However, there was no significant difference in CXCL12-mediated inositol phosphate metabolism in laryngeal cancer. Immune cell infiltration analysis revealed a higher proportion of macrophages in laryngeal and lung cancer tissues compared to non-tumor tissues. Conclusion: We found that gene mutations, transcription factors, and miRNA coordination play a crucial role in this process. Additionally, we found that the cell and immune cells present in the tissues of laryngeal cancer patients contribute to the metabolism of inositol phosphate metabolism, thereby promoting the occurrence of lung cancer.