Objective To compare DEGs between primary and metastatic lesions in lung adenocarcinoma patients with positive ALK fusion gene, and to explore the mechanism of drug-resistance and the potential drug targets in metastatic lesions of lung adenocarcinoma patients.

Methods GSE125864 was obtained from GEO database. According to the different sampling sites of tumor tissue, two groups were divided: primary tumor lesions group and metastatic tumor lesions group. The DEGs between the two groups were compared, and the differences in biological functions and enrichment signaling pathways of these DEGs were analyzed. The protein-protein interaction network was constructed and applied to screen hub genes. Based on TCGA and cancer treatment response portal database, the prognosis and drug target prediction of the 10 key cores were analyzed.

Results In total, 227 DEGs were identified, with 134 upregulated DEGs and 93 downregulated DEGs in the metastatic tumor lesions group, compared with primary tumor lesions group. GO and KEGG enrichment analyses showed that the functions of these DEGs were mainly involved in complement and coagulation cascade, chemical carcinogenesis and retinol metabolism pathways. The top 10 hub genes with the highest degree were analyzed in the protein-protein interaction network. The expression of HRG and AHSG genes were associated with poor prognosis of lung adenocarcinoma patients, and SERPINC1, HRG, ApoA1, FGA and FGG genes were correlated with a variety of potential small molecule drugs.

Conclusion The molecular functions and signaling pathways involved in DEGs may induce drug-resistance in metastatic ALK-positive lung adenocarcinoma patients.