TY - JOUR
T1 - RNA-Seq Analysis of Colorectal Tumor-Infiltrating Myeloid-Derived Suppressor Cell Subsets Revealed Gene Signatures of Poor Prognosis
AU - Saleh, Reem
AU - Sasidharan Nair, Varun
AU - Al-Dhaheri, Mahmood
AU - Khawar, Mahwish
AU - Abu Nada, Mohamed
AU - Alajez, Nehad M.
AU - Elkord, Eyad
N1 - Publisher Copyright:
© Copyright © 2020 Saleh, Sasidharan Nair, Al-Dhaheri, Khawar, Abu Nada, Alajez and Elkord.
PY - 2020/11/10
Y1 - 2020/11/10
N2 - Elevated levels of myeloid-derived suppressor cells (MDSCs), including polymorphonuclear MDSCs (PMN-MDSCs) and immature MDSCs (I-MDSCs), are usually associated with disease progression in cancer patients, including colorectal cancer (CRC). However, biological mechanisms and molecular pathways regulated by MDSC subpopulations in the CRC tumor microenvironment (TME) have not been fully investigated. In this study, we performed transcriptomic analysis of tumor-infiltrating I-MDSCs and PMN-MDSCs isolated from tumor tissues of six CRC patients, compared to antigen-presenting cells (APCs). We also compared the transcriptomic profiles of tumor-infiltrating PMN-MDSCs to I-MDSCs. Our results showed different molecular pathways regulated by each MDSC subset, potentially reflecting their phenotypical/molecular/functional characteristics in the CRC TME. Moreover, we identified gene signatures in PMN-MDSC and I-MDSC of poor overall survival (OS) and disease-free survival (DFS) using the Cancer Genome Atlas (TCGA) dataset from patients with colon adenocarcinoma (COAD). However, functional studies are required to validate these findings.
AB - Elevated levels of myeloid-derived suppressor cells (MDSCs), including polymorphonuclear MDSCs (PMN-MDSCs) and immature MDSCs (I-MDSCs), are usually associated with disease progression in cancer patients, including colorectal cancer (CRC). However, biological mechanisms and molecular pathways regulated by MDSC subpopulations in the CRC tumor microenvironment (TME) have not been fully investigated. In this study, we performed transcriptomic analysis of tumor-infiltrating I-MDSCs and PMN-MDSCs isolated from tumor tissues of six CRC patients, compared to antigen-presenting cells (APCs). We also compared the transcriptomic profiles of tumor-infiltrating PMN-MDSCs to I-MDSCs. Our results showed different molecular pathways regulated by each MDSC subset, potentially reflecting their phenotypical/molecular/functional characteristics in the CRC TME. Moreover, we identified gene signatures in PMN-MDSC and I-MDSC of poor overall survival (OS) and disease-free survival (DFS) using the Cancer Genome Atlas (TCGA) dataset from patients with colon adenocarcinoma (COAD). However, functional studies are required to validate these findings.
KW - colorectal cancer
KW - immune responses
KW - metabolism
KW - myeloid-derived suppressor cells
KW - signaling pathways
KW - transcriptomic profiling
UR - http://www.scopus.com/inward/record.url?scp=85097064794&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.604906
DO - 10.3389/fonc.2020.604906
M3 - Article
AN - SCOPUS:85097064794
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 604906
ER -