We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Integrin-linked kinase pathway in heterogeneous pulmonary sarcomatoid carcinoma.
- Authors
Shimizu, Shigeki; Sakai, Kazuko; Chikugo, Takaaki; Satou, Takao; Shiraishi, Naoki; Mitsudomi, Tetsuya; Nishio, Kazuto
- Abstract
Pulmonary sarcomatoid carcinoma (PSC) is classified as poorly differentiated, and non-small cell lung carcinomas that contained a component of sarcoma or sarcoma-like differentiation are rare. The underlying carcinogenetic mechanism governing PSC remains unclear. The current study investigated the underlying carcinogenetic mechanism of PSC based on the hypothesis that it involves the epithelial-mesenchymal transition (EMT) process. Mutation analysis of PSCs, including carcinosarcoma, pleomorphic carcinoma and epithelial carcinoma specimens, was performed using targeted deep sequencing, whole transcriptome analysis and digital spatial profiling (DSP). PSCs exhibit a distinct mutation profile, with TP53, SYNE1 and APC mutations. Therefore, clustering of the gene expression profiles allowed the PSCs to be distinguished from the epithelial carcinomas. Increased gene expression of fibronectin in PSC was an important contributor to differential profiles. Pathway analysis revealed enhanced activity of the integrin-linked kinase (ILK) signaling pathway in the PSCs. DSP analysis using 56 antibodies of marker proteins confirmed significantly higher expression of fibronectin in PSCs. Intratumor heterogeneity of fibronectin expression was observed in sarcoma components. In conclusion, epithelial-mesenchymal transition process mediated by ILK signaling may be associated with carcinogenetic mechanisms of PSC. Overexpression of fibronectin mediated by ILK signaling appears to serve a role in the EMT involved in the PSC transformation process.
- Subjects
CARCINOSARCOMAS; RNA sequencing; GENE expression profiling; EPITHELIAL-mesenchymal transition; CARCINOMA; FIBRONECTINS
- Publication
Oncology Letters, 2021, Vol 21, Issue 4, pN.PAG
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2021.12582