Transcriptomic profiling of single circulating tumor cells provides insight into human metastatic gastric cancer

Ryo Negishi,Hitomi Yamakawa,Fumiaki Koizumi,Mayuko Horikawa,Takeru Kobayashi,Tadashi Matsunaga,Tomoko Yoshino,Takeshi Sawada,Yusuke Kanemasa,Akihiko Kageyama,Keisuke Oboki,Tatsu Shimoyama,Yasushi Omuro,Tsuyoshi Tanaka,Chikako Funasaka

doi:10.1038/s42003-021-02937-x

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.

Highlights

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
CTCs at the single-cell level has shown that CTCs are a heterogeneous population between and within patient groups. This may be due to cells undergoing epithelial-mesenchymal transition (EMT); both epithelial and mesenchymal cell types have been identified in CTCs10,11
Transcriptome analysis of single CTCs has only been reported in small-scale clinical trials for a limited number of cancer types, such as breast[10,13,14,15], hepatocellular[16,17], and prostate cancer[7,18,19] and multiple myeloma[20,21], and there is a need to expand this investigation to a variety of cancer types

Summary

Introduction

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. 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. Transcriptome analysis of CTCs at the single-cell level has shown that CTCs are a heterogeneous population between and within patient groups. This may be due to cells undergoing epithelial-mesenchymal transition (EMT); both epithelial and mesenchymal cell types have been identified in CTCs10,11. Transcriptome analysis of single CTCs has only been reported in small-scale clinical trials for a limited number of cancer types, such as breast[10,13,14,15], hepatocellular[16,17], and prostate cancer[7,18,19] and multiple myeloma[20,21], and there is a need to expand this investigation to a variety of cancer types

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Conclusion