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

Abstract

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.

Highly Expressed SPC25 Promotes the Stemness, Proliferation and EMT of Oral Squamous Cell Carcinoma Cells via Modulating the TGF-β Signaling Pathway

“…In OSCC, the prognostic value of TGF-β1 has still remained elusive. Nevertheless, there is a correlation between TGF-β1 signaling pathway and SPC25 expression levels 24) . Our data showed that silencing of SPC25 suppressed the TGF-β1/Smad signaling pathway, as evidenced by downregulated expression levels of TGF-β1, p-smad2, and p-smad3.…”

“…Upregulation of SPC25 expression levels was reported in prostate, lung, and breast cancer cells, and it significantly promoted the proliferation of these tumor cells [16][17][18][19]22) . SPC25 was engaged in the regulation of cell stemness 18) , proliferation 23) , and EMT 24) . A correlation was previously found between TGF-β1 signaling pathway and SPC25 expression levels 24) .…”

“…SPC25 was engaged in the regulation of cell stemness 18) , proliferation 23) , and EMT 24) . A correlation was previously found between TGF-β1 signaling pathway and SPC25 expression levels 24) . However, the detailed expression level and the biological functions of SPC25 in OSCC cells have still remained elusive.…”