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

Laryngeal cancer, a prevalent malignant tumor, frequently leads to mortality through the development of second primary lung cancer (SPLC). To investigate the potential mechanisms underlying SPLC development in laryngeal cancer patients, we conducted an integrated multi-omics analysis. We obtained laryngeal cancer (GSE51985) and lung cancer (GSE102287) datasets from the gene expression omnibus and identified differentially expressed genes using the "limma" package. Our analysis revealed 9 shared genes, with UBE2C, POLQ, RAD51, and HOXB7 being up-regulated and EDNRB, GPD1L, F10, SORBS2, and CXCL12 down-regulated in both cancers. Functional enrichment analysis indicated these genes were primarily involved in pathways in cancer and the cell cycle. We further constructed transcription factor (TF)-miRNA-gene interaction networks, identifying 120 TFs and 246 miRNAs coordinating these shared genes. Metabolic analysis linked CXCL12 to inositol phosphate metabolism, and single-cell RNA sequencing from datasets GSE150321 and GSE127471 demonstrated that intermediate monocytes in lung cancer were highly active in this metabolic pathway. Additionally, immune cell infiltration analysis using CIBERSORT revealed a higher proportion of macrophages in both cancer types compared to non-tumor tissues. In conclusion, our study suggests that shared genetic alterations, regulated by specific TFs and miRNAs, alongside an altered immune microenvironment and CXCL12-mediated inositol phosphate metabolism likely driven by intermediate monocytes, contribute to the development of SPLC following laryngeal cancer.