Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Abstract Background: Lung adenocarcinoma with ground-glass opacity (GGO) has been detected increasingly and now accounts for most lung cancer patients. Lung adenocarcinoma with GGO contains a complex ecosystem. The mechanism of lung adenocarcinoma with GGO remains largely elusive. We use mass spectrometry proteomics combined with metabolomics to understand how these characteristics achieve a long-term functional balance and the trend of changes in tumor progression at the cellular functional level. Methods: We initiated a prospective cohort study to characterize lung adenocarcinoma with GGO components or without GGO components. Tumor and para-cancer tissue samples were collected. Multi-omics including transcriptomics proteomics and metabonomics were performed. Results: We found lung adenocarcinoma with GGO had a relatively slow proliferation tumor cells and stronger immune cell infiltration in proteomic and transcriptomic analysis. The immune cell markers expression, including CD47, CD68, CD81, CD86, C1Q, SPP1, CXCL13, ALOX5AP and HPGD was found overexpression in lung adenocarcinoma with GGO, which indicated more immune cell infiltration. In metabolomic analysis, GAPDH, ENO1 and LDHA were highly expressed in pure-solid lung adenocarcinoma, and GPD1 was highly expressed in lung adenocarcinoma with GGO. The combined transcriptome and proteome analysis revealed that proteins with consistent differences mainly included GAPDH, MKI67, AGER, and CRYM. KEGG pathway enrichment analysis showed that several aliphatic acyclic compounds expression were higher in lung adenocarcinoma with GGO. Conclusion: We describe a functional homeostasis in lung adenocarcinoma with GGO, which was constructed by relatively slow proliferation tumor cells and stronger immune cell infiltration. Overexpression of CXCL13 drives the infiltration of immune cells, which means the formation of anti-tumor tertiary lymphatic structures. The dysfunction of macrophage may be an important marker of this progression.