Abstract 1602: Genomic profiling of lung cancer associated with idiopathic pulmonary fibrosis

Abstract

Abstract Idiopathic pulmonary fibrosis (IPF) is reportedly associated with an increased risk of lung cancer. However, optimal diagnosis and treatment for lung cancer associated with IPF remains unclear. In this study, we aimed to clarify the mechanism of carcinogenesis and progression in lung cancer with IPF. We used tumor tissues and adjacent non-tumor lung tissues from 29 lung cancer patients who had undergone complete surgical resection at Nippon Medical School Hospital between 2013 and 2017. Whole-Exon Sequencing was performed on 29 paired samples, consisted of 19 lung cancers with IPF (IPF group) and 10 lung cancers with normal lung (non-IPF group). The candidate gene alterations discriminating between the IPF and non-IPF group, were identified using the random-forest method, RelifF method along with the data from Catalogue Of Somatic Mutations In Cancer (COSMIC). Twenty-five gene alterations were specifically found in IPF tissues and/or tumor tissues with IPF. Whenever 5 of 25 genes including MUC2 and TTF1, were altered in both IPF tissues and tumor tissues, 20 of 25 genes including CADM1, were altered in only tumor tissues. We are undergoing the validation study using other tissues in independent cohorts. Among the candidate genes, Cell adhesion molecule genes (CADM1) gene alterations were frequently found in 15 out of 19 in only tumor tissues with IPF. The CADM1 protein expression was decreased in tumors than in non-tumor fibrotic tissues by western blotting. The CADM1 induced the epithelial-mesenchymal transition (EMT) on the multifunctional cell process involved in the pathogenesis of fibrosis in vitro study. Whenever the down-regulation of CADM1 was frequently detected in various human cancers through its allelic loss as well as hypermethylation within promoter region in addition to inactivate gene mutation, the up-regulation of CADM1 was frequently detected in paired IPF tissues. The CADM1 may be a target candidate in lung cancer associated with IPF. Citation Format: Rintaro Noro, Akihiko Miyanaga, Aya Fukuizumi, Shinobu Kunugi, Teppei Sugano, Miwako Omori, Yuji Minegish, Jitsuo Usuda, Masahiro Seike, Kaoru Kubota, Mamiko Hirao, Kuniko Matsuda, Akihiko Gemma. Genomic profiling of lung cancer associated with idiopathic pulmonary fibrosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1602.