Author ORCID Identifier
0009-0009-7825-3861
Date of Graduation
8-2024
Document Type
Thesis (MS)
Program Affiliation
Quantitative Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
John Paul Shen, M.D.
Committee Member
Linghua Wang, M.D., Ph.D.
Committee Member
Wenyi Wang, Ph.D.
Committee Member
Kadir C. Akdemir, Ph.D.
Committee Member
Wenbo Li, PhD
Abstract
Colorectal cancer Colorectal Cancer (CRC) is the leading cause of cancer-related deaths, with the majority of these deaths occurring after metastases. In this study, we used single-cell RNA transcriptome sequencing to characterize the cellular and molecular features of primary CRC and colorectal liver metastases (CRLM). Analysis of 130 samples revealed significant heterogeneity in the tumor microenvironment (TME) characterized by a diversity of cancer-associated fibroblasts, immune cells, and endothelial cell populations. Notably, we identified different CAF subtypes, including inflammatory (iCAFs), matrix(mCAFs), complement (cCAFs), and vascular (vCAFs). iCAFs were enriched in primary tumors expressing higher levels of inflammation-associated genes, whereas mCAFs were enriched in liver metastatic CRC, which may promote tumor cell proliferation via the Epithelial-Mesenchymal Transition (EMT) pathway. Immune cell analysis highlighted significant differences in the proportion and functional status between primary and metastatic sites. Correlation analyses suggest that there may be crosstalk between CAFs and immune cells that influence the immune microenvironment and metastasis. This comprehensive CRC and CRLM single-cell atlas provide valuable information to understand the pro-metastasis components and provides insights into drug development to improve patient prognosis.
Keywords
colorectal cancer; Single-cell transcriptomics; Cancer associated fibroblast;Immune environment