Biomarker Identification via Spatial Transcriptomics Profiling of Colorectal Cancer and Colorectal Cancer with Liver...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Colorectal cancer (CRC) outcomes worsen with recurrence and metastasis.
• Cancer stem cells (CSCs) are implicated in CRC recurrence, metastasis, and treatment resistance.

Purpose of the Study:

• To identify CSC-associated biomarkers in CRC using spatial transcriptomics.
• To evaluate the functional role of identified biomarkers in CRC progression.

Main Methods:

• Spatial transcriptomic profiling of normal, primary CRC, and metastatic tissues.
• CRISPR-Cas9 gene editing to create CCN2-knockout cell lines.
• Immunohistochemical analysis of tissue microarrays.

Main Results:

• CCN2 was enriched in primary CRC CSCs; APOC2 was upregulated in liver-metastatic CSCs.
• Loss of CCN2 reduced CRC cell proliferation, migration, invasion, and oxaliplatin resistance.
• CCN2 expression correlated positively with CSC markers SOX2 and Nestin.

Conclusions:

• CCN2 is a key regulator of stemness and malignant potential in CRC.
• CCN2 represents a potential therapeutic target for preventing CRC recurrence and metastasis.
• Further research is needed to explore CCN2 pathways and APOC2's role in metastatic CRC.