In IPF-LC, the mutation frequencies of CADM1 and SPC25 were 47% and 53%, respectively. About one-third of the cases had both mutations. Pathway analysis indicated that these genes are involved in the TGF-β1 signaling pathway. Mutations decreased CADM1 expression and increased SPC25 expression, promoting epithelial-to-mesenchymal transition and cell proliferation in lung cancer cells. Paclitaxel and DNMT1 inhibitors inhibited SPC25 expression. This evidence concerns the gene CADM1 and lung cancer.