Affiliations: [a] Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China | [b] Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China | [c] Institute of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China | [d] Department of Thoracic Surgery, Dezhou City Second People’s Hospital, Dezhou, Shandong, China | [e] Medical Department, OrigiMed, Shanghai, China | [f] OrigiMed, Shanghai, China
Correspondence:
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Corresponding author: Jiajun Du, Department of Thoracic Surgery and Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong 250021, China. Tel.: +86 0531 6877 7100; E-mail: [email protected].
Note: [1] Guanghui Wang and Fenglong Bie contributed equally to this work.
Abstract: BACKGROUND: Metastasis regularly is a marker of the disease development of cancers. Some metastatic sites significantly showed more serious clinical outcomes in non-small cell lung cancer (NSCLC). Whether they are caused by tissue-specific (TS) or non-tissue-specific (NTS) mechanisms is still unclear. OBJECTIVE: Explore co-expression gene modules of non-small cell lung cancer metastases. METHODS: Weighted Correlation Network Analysis (WGCNA) was used to identify the gene modules among the metastases of NSCLC. The clinical significance of those gene modules was evaluated with the Cox hazard proportional model with another independent dataset. Functions of each gene module were analyzed with gene ontology. Typical genes were further studied. RESULTS: There were two TS gene modules and two NTS gene modules identified. One TS gene module (green module) and one NTS gene module (purple module) significantly correlated with survival. This NTS gene module (purple module) was significantly enriched in the epithelial-to-mesenchymal transition (EMT) process. Higher expression of the typical genes (CA14, SOX10, TWIST1, and ALX1) from EMT process was significantly associated with a worse survival. CONCLUSION: The lethality of NSCLC metastases was caused by TS gene modules and NTS gene modules, among which the EMT-related gene module was critical for a worse clinical outcome.
