Integrated multi-omics analysis for lung adenocarcinoma in Xuanwei, China

Background: Xuanwei lung cancer (XWLC) is well-known for its high incidence and mortality. However, the molecular mechanism is still unclear. Methods: We performed a comprehensive transcriptomic, proteomic, and phosphoproteomic characterization of tumors and matched normal adjacent tissues from three XWLC patients with lung adenocarcinoma (LUAD). Results: Integrated transcriptome and proteome analysis revealed dysregulated molecules and pathways in tumors and identified enhanced metabolic-disease coupling. Non-coding RNAs were widely involved in posttranscriptional regulatory mechanisms to coordinate the progress of LUAD and partially explained the molecular differences between RNA and protein expression patterns. Phosphoproteome provided evidence support for new phosphate sites, reporting the potential roles of core kinase family members and key kinase pathways involved in metabolism, immunity, and homeostasis. In addition, by comparing with the previous LUAD researches, we emphasized the higher degree of oxidative phosphorylation in Xuanwei LUAD and pointed that VIPR1 deficiency aggravated metabolic dysfunction. Conclusion: Our integrated multiomics analysis provided a powerful resource for a systematic understanding of the molecular structure of XWLC and proposed therapeutic opportunities based on redox metabolism.