TY - JOUR
T1 - Redefining tumor classification and clinical stratification through a colorectal cancer single-cell atlas
AU - Khaliq, Ateeq M.
AU - Kurt, Zeyneb
AU - Grunvald, Miles W.
AU - Erdogan, Cihat
AU - Turgut, Sultan Sevgi
AU - Rand, Tim
AU - Khare, Sonal
AU - Borgia, Jeffrey A.
AU - Hayden, Dana M.
AU - Pappas, Sam G.
AU - Govekar, Henry R.
AU - Bhama, Anuradha R,
AU - Singh, Ajaypal
AU - Jacobson, Richard A.
AU - Kam, Audery E.
AU - Zloza, Andrew
AU - Reiser, Jochen
AU - Catenacci, Daniel V.
AU - Turaga, Kiran
AU - Radovich, Milan
AU - Thyparambil, Sheeno
AU - Levy, Mia A.
AU - Subramanian, Janakiraman
AU - Kuzel, Timothy M.
AU - Sadanandam, Anguraj
AU - Hussain, Arif
AU - El-Rayes, Bassel
AU - Salahudeen, Ameen
AU - Masood, Ashiq
PY - 2021/2/7
Y1 - 2021/2/7
N2 - Colorectal cancer (CRC), a disease of high incidence and mortality, exhibits a large degree of inter- and intra-tumoral heterogeneity. The cellular etiology of this heterogeneity is poorly understood. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes that significantly stratifies overall survival in more than 1,500 CRC patients with bulk transcriptomic data. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development. Competing Interest Statement: The authors have declared no competing interest.
AB - Colorectal cancer (CRC), a disease of high incidence and mortality, exhibits a large degree of inter- and intra-tumoral heterogeneity. The cellular etiology of this heterogeneity is poorly understood. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes that significantly stratifies overall survival in more than 1,500 CRC patients with bulk transcriptomic data. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development. Competing Interest Statement: The authors have declared no competing interest.
UR - https://www.mendeley.com/catalogue/427ca7f7-036d-32c9-91fc-3f9ac073accb/
U2 - 10.1101/2021.02.02.429256
DO - 10.1101/2021.02.02.429256
M3 - Article
JO - bioRxiv
JF - bioRxiv
M1 - 429256
ER -