The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Li Wang; Wangyang Liu; Kailai Liu; Lixia Wang; Xiangzhe Yin; Lin Bo; Haotian Xu; Shihua Lin; Ke Feng; Xinyu Zhou; Lin Lin; Meiting Fei; Caiyu Zhang; Shangwei Ning; Hongying Zhao

doi:10.1016/j.omtn.2022.11.019

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Mol Ther Nucleic Acids. 2022 Nov 22:30:633-647. doi: 10.1016/j.omtn.2022.11.019. eCollection 2022 Dec 13.

Authors

Li Wang¹, Wangyang Liu¹, Kailai Liu¹, Lixia Wang¹, Xiangzhe Yin¹, Lin Bo¹, Haotian Xu¹, Shihua Lin¹, Ke Feng¹, Xinyu Zhou¹, Lin Lin¹, Meiting Fei¹, Caiyu Zhang¹, Shangwei Ning¹, Hongying Zhao¹

Affiliation

¹ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Abstract

Brain metastasis occurs in approximately 30% of patients with lung adenocarcinoma (LUAD) and is closely associated with poor prognosis, recurrence, and death. However, dynamic gene regulation and molecular mechanism driving LUAD progression remain poorly understood. In this study, we performed a comprehensive single-cell transcriptome analysis using data from normal, early stage, advanced stage, and brain metastasis LUAD. Our single-cell-level analysis reveals the cellular composition heterogeneity at different stages during LUAD progression. We identified stage-specific risk genes that could contribute to LUAD progression and metastasis by reprogramming immune-related and metabolic-related functions. We constructed an early advanced metastatic dysregulated network and revealed the dynamic changes in gene regulations during LUAD progression. We identified 6 early advanced (HLA-DRB1, HLA-DQB1, SFTPB, SFTPC, PLA2G1B, and FOLR1), 8 advanced metastasis (RPS15, RPS11, RPL13A, RPS24, HLA-DRB5, LYPLA1, KCNJ15, and PSMA3), and 2 common risk genes in different stages (SFTPD and HLA-DRA) as prognostic markers in LUAD. Particularly, decreased expression of HLA-DRA, HLA-DRB1, HLA-DQB1, and HLA-DRB5 refer poor prognosis in LUAD by controlling antigen processing and presentation and T cell activation. Increased expression of PSMA3 and LYPLA1 refer poor prognosis by reprogramming fatty acid metabolism and RNA catabolic process. Our findings will help further understanding the pathobiology of brain metastases in LUAD.

Keywords: MT: Bioinformatics; biological function; cancer dynamic network; lung adenocarcinoma; prognosis; tumor heterogeneity.