Transcriptomic Analysis Identifies Complement Component 3 as a Potential Predictive Biomarker for Chemotherapy...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• FOLFOX chemotherapy is a standard treatment for colorectal cancer (CRC).
• Drug resistance to FOLFOX limits treatment efficacy and patient survival.
• Identifying genes associated with FOLFOX resistance is crucial for understanding treatment failure.

Purpose of the Study:

• To identify key genes associated with FOLFOX resistance and recurrence in colorectal cancer.
• To elucidate the biological mechanisms and prognostic implications of identified genes.

Main Methods:

• Utilized transcriptomic data from TCGA, GEO, and in-house microarrays.
• Applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes.
• Conducted survival, immune cell infiltration, and pathway analyses.

Main Results:

• Complement component 3 (C3) was identified as a crucial hub gene linked to FOLFOX resistance and CRC recurrence.
• High C3 expression correlated with poorer survival outcomes (progression-free, disease-free, recurrence-free).
• C3 expression showed a negative association with oxaliplatin sensitivity and influenced the tumor microenvironment, promoting invasion and metastasis.

Conclusions:

• Elevated C3 expression is a significant factor in FOLFOX chemotherapy resistance, especially impacting oxaliplatin efficacy.
• C3 may serve as a predictive biomarker for guiding treatment strategies in colorectal cancer.