Cell-of-Origin Analysis of Metastatic Gastric Cancer Uncovers the Origin of Inherent Intratumor Heterogeneity and a Fundamental Prognostic Signature
Year: 2019
Type: preprint
Study design: Observational Study
Abstract: Intra-tumoral heterogeneity (ITH) is the fundamental property of cancer, however, the origin of ITH remains poorly understood. Here we performed single-cell RNA sequencing of peritoneal carcinomatosis (PC) from 20 patients with advanced gastric adenocarcinoma (GAC), constructed a transcriptome map of 45,048 PC cells, determined the cell-of-origin of each tumor cell, and incisively explored ITH of PC tumor cells at single-cell resolution. The links between cell-of-origin and ITH was illustrated at transcriptomic, genotypic, molecular, and phenotypic levels. This study characterized the origins of PC tumor cells that populate and thrive in the peritoneal cavity, uncovered the diversity in tumor cell-of-origins and defined it as a key determinant of ITH. Furthermore, cell-of-origin-based analysis classified PC into two cellular subtypes that were prognostic independent of clinical variables, and a 12-gene prognostic signature was then derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis/progression and could be practical for patient stratification.
DOI: 10.1101/725390
Authors: Ruiping Wang, Shumei Song, Kazuto Harada, Guangchun Han, Melissa Pool Pizzi, Meina Zhao, Ghia Tatlonghari, Shaojun Zhang, Yuanxin Wang, Shuangtao Zhao, Brian D. Badgwell, Mariela Blum Murphy, Namita Shanbhag, Jeannelyn S. Estrella, Sinchita Roy-Chowdhuri, Ahmed Adel Fouad Abdelhakeem, Guang Peng, George A. Calin, Samir Hanash, Alexander J. Lazar, Andrew Futreal, Jaffer A. Ajani, Linghua Wang
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2966819902