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Clinical Significance of Circulating Tumor Cell Induced Epithelial-Mesenchymal Transition in Patients with Metastatic Colorectal Cancer by Single-Cell RNA-Sequencing
| Content Provider | MDPI |
|---|---|
| Author | Kozuka, Masahiro Battaglin, Francesca Jayachandran, Priya Wang, Jingyuan Arai, Hiroyuki Soni, Shivani Zhang, Wu Hirai, Mitsuharu Matsusaka, Satoshi Lenz, Heinz-Josef |
| Copyright Year | 2021 |
| Description | Background: Circulating tumor cells (CTCs) are a prognostic marker in patients with metastatic colorectal cancer (mCRC). However, little is known about the characterization of CTCs in mCRC at the single-cell level using RNA sequencing. The purpose of this study was to validate the capability to detect and isolate single CTCs for single-cell RNA sequencing (scRNA-seq) and to identify clinical significance at a single CTC level. Methods: Single CTCs from 27 mCRC patients were collected by CTC-FIND, which is comprised of filter separation and immunomagnetic depletion to collect ultra-pure CTC samples. To address tumor heterogeneity, CTCs were collected without relying on any traditional CTC markers, such as epithelial and mesenchymal cell antigens, and were undertaken by scRNA-seq using SMART-Seq v4. Results: We identified 59 single CTCs which were classified into four groups by epithelial, epithelial-mesenchymal transition (EMT) and stem cell-related gene expression. Patients receiving second or later-line treatment who had EMT gene expressing CTCs had a significantly shorter PFS and OS. Conclusions: Exploiting CTC-FIND with SMART-Seq v4 showed that scRNA-seq of CTCs may shed new insight into tumor heterogeneity of mCRC and that the presence of CTCs expressing EMT-related genes at the single-cell level could have prognostic value in mCRC patients. |
| Starting Page | 4862 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13194862 |
| Journal | Cancers |
| Issue Number | 19 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-09-28 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Circulating Tumor Cell Single-cell Rna-sequencing Epithelial-mesenchymal Transition Colorectal Cancer |
| Content Type | Text |
| Resource Type | Article |