Identification of Colorectal Cancer Cell Stemness from Single-Cell RNA Sequencing.

Area of Science:

• Oncology
• Genomics
• Cell Biology

Background:

• Colorectal cancer stem cells (CSCs) are crucial for metastasis, relapse, and treatment resistance.
• Existing markers for CSCs show heterogeneity and limited utility at the single-cell level.

Purpose of the Study:

• To identify colorectal CSCs at the single-cell level using RNA sequencing.
• To develop a robust stemness signature for colorectal CSCs.

Main Methods:

• Single-cell RNA sequencing was performed on primary colon tumors, liver metastases, and normal tissues.
• A novel single-cell stemness signature (SCS_sig) was developed to identify colorectal CSCs.
• Stemness levels were quantified and correlated with patient survival data.

Main Results:

• Classical CSC markers showed poor alignment in single-cell data.
• The novel SCS_sig effectively identified colorectal CSCs.
• Tumor cells exhibited a stemness continuum, unlike the bimodal distribution in normal cells, indicating greater plasticity.
• Higher SCS_sig scores were significantly associated with shorter disease-free survival.

Conclusions:

• The developed stemness signature provides a more accurate method for identifying colorectal CSCs at the single-cell level.
• Tumor cell stemness is a continuum, suggesting plasticity that may contribute to colorectal cancer progression.
• Increased stemness in colorectal cancer is linked to a higher risk of relapse.