CADM1 and SPC25 Gene Mutations in Lung Cancer Patients With Idiopathic Pulmonary Fibrosis

Abstract

IntroductionTo investigate the genomic profiles of patients with lung cancer with idiopathic pulmonary fibrosis (IPF-LC), mechanism of carcinogenesis, and potential therapeutic targets. MethodsWe analyzed 29 matched, surgically resected, cancerous and noncancerous 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 of the Tokyo University of Science. ResultsIn IPF-LC, CADM1 and SPC25 were mutated at a frequency of 47% (9 of 19) and 53% (10 of 19), respectively. Approximately one-third of the IPF-LC cases (7 of 19; 36%) had both mutations. Pathway analysis revealed that these two genes are involved in transforming growth factor-β1 signaling. CADM1 and SPC25 gene mutations decreased the expression of CADM1 and increased that of SPC25 revealing transforming growth factor-β1–induced epithelial-to-mesenchymal transition and cell proliferation in lung cancer cells. Furthermore, treatment with paclitaxel and DNMT1 inhibitor suppressed SPC25 expression. ConclusionsCADM1 and SPC25 gene mutations may be novel diagnostic markers and therapeutic targets for IPF-LC.