CADM1 and SPC25 gene mutations in lung cancer patients with idiopathic pulmonary fibrosis

Abstract Introduction This study investigated the genomic profiles of lung cancer patients with idiopathic pulmonary fibrosis (IPF-LC), mechanism of carcinogenesis, and potential therapeutic targets. Methods We analyzed 29 matched, surgically resected, cancerous/non-cancerous lung tissues (19 IPF-LC and 10 non-IPF-LC) by whole exome sequencing and bioinformatics analysis, and established a medical-engineering collaboration with the department of engineering. Results In IPF-LC, cell adhesion molecule 1 (CADM1) and spindle component 25 (SPC25) were mutated at a frequency of 47% (9/19) and 53% (10/19), respectively. Approximately one-third (7/19; 36%) of IPF-LC cases had both mutations. Pathway analysis revealed that these two genes are involved in transforming growth factor-β1 (TGF-β1) signaling. CADM1 and SPC25 gene mutations decreased the expression of CADM1 and increased that of SPC25 showing TGF-β1-induced epithelial-to-mesenchymal transition and cell proliferation in lung cancer cells. Furthermore, treatment with paclitaxel and DNA methyltransferase 1 (DNMT1) inhibitor suppressed SPC25 expression. Conclusion CADM1 and SPC25 gene mutations may be novel diagnostic markers and therapeutic targets for IPF-LC.