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

Aya Fukuizumi, MD; Rintaro Noro, MD, PhD; Masahiro Seike, MD, PhD; Akihiko Miyanaga, MD, PhD; Yuji Minegishi, MD, PhD; Miwako Omori, MD; Mamiko Hirao; Kuniko Matsuda; Shinobu Kunugi, MD, PhD; Kazutaka Nishiwaki; Masahiro Morimoto; Haruka Motohashi; Hayato Ohwada, PhD; Jitsuo Usuda, MD, PhD; Akihiko Gemma, MD, PhD

JTO Clinical and Research Reports (Nov 2021)

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

Aya Fukuizumi, MD,
Rintaro Noro, MD, PhD,
Masahiro Seike, MD, PhD,
Akihiko Miyanaga, MD, PhD,
Yuji Minegishi, MD, PhD,
Miwako Omori, MD,
Mamiko Hirao,
Kuniko Matsuda,
Shinobu Kunugi, MD, PhD,
Kazutaka Nishiwaki,
Masahiro Morimoto,
Haruka Motohashi,
Hayato Ohwada, PhD,
Jitsuo Usuda, MD, PhD,
Akihiko Gemma, MD, PhD

Affiliations

Aya Fukuizumi, MD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Rintaro Noro, MD, PhD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Masahiro Seike, MD, PhD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Corresponding author. Address for correspondence: Masahiro Seike, MD, PhD, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Akihiko Miyanaga, MD, PhD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Yuji Minegishi, MD, PhD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Miwako Omori, MD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Mamiko Hirao: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Kuniko Matsuda: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Shinobu Kunugi, MD, PhD: Department of Analytic Human Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Kazutaka Nishiwaki: Department of Industrial Administration, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan
Masahiro Morimoto: Department of Industrial Administration, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan
Haruka Motohashi: Department of Industrial Administration, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan
Hayato Ohwada, PhD: Department of Industrial Administration, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan
Jitsuo Usuda, MD, PhD: Department of Thoracic Surgery, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Akihiko Gemma, MD, PhD: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

Journal volume & issue: Vol. 2, no. 11
p. 100232

Abstract

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Introduction: To investigate the genomic profiles of patients with lung cancer with idiopathic pulmonary fibrosis (IPF-LC), mechanism of carcinogenesis, and potential therapeutic targets. Methods: We 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. Results: In 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. Conclusions: CADM1 and SPC25 gene mutations may be novel diagnostic markers and therapeutic targets for IPF-LC.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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