Shuangjie You (Advisor: John Paul Shen, PhD)

Delineating Metastasis in MSS Colorectal Cancer by Single-Cell RNA Sequencing 

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.

Advisory Committee:

• John Paul Shen, MD, Chair
• Kadir Akdemir, PhD
• Wenbo Li, PhD
• Linghua Wang, MD, PhD
• Wenyi Wang, PhD 

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