Transcriptomic profiling of single circulating tumor cells provides insight into human metastatic gastric cancer
Ryo Negishi, Hitomi Yamakawa, Takeru KOBAYASHI, Mayuko Horikawa, Tatsu Shimoyama, Fumiaki Koizumi, Takeshi Sawada, Keisuke Oboki, Yasushi Omuro, Chikako Funasaka, Akihiko Kageyama, Yusuke Kanemasa, Tsuyoshi Tanaka, Tadashi Matsunaga, Tomoko Yoshino
Abstract
Transcriptome analysis of circulating tumor cells (CTCs), which migrate into blood vessels from primary tumor tissues, at the single-cell level offers critical insights into the biology of metastasis and contributes to drug discovery. However, transcriptome analysis of single CTCs has only been reported for a limited number of cancer types, such as multiple myeloma, breast, hepatocellular, and prostate cancer. Herein, we report the transcriptome analysis of gastric cancer single-CTCs. We utilized an antigen-independent strategy for CTC isolation from metastatic gastric cancer patients involving a size-dependent recovery of CTCs and a single cell isolation technique. The transcriptomic profile of single-CTCs revealed that a majority of gastric CTCs had undergone epithelial-mesenchymal transition (EMT), and indicated the contribution of platelet adhesion toward EMT progression and acquisition of chemoresistance. Taken together, this study serves to employ CTC characterization to elucidate the mechanisms of chemoresistance and metastasis in gastric cancer.