Micronuclei in Circulating Tumor Associated Macrophages Predicts Progression in Advanced Colorectal Cancer

Area of Science:

• Oncology
• Genetics
• Cell Biology

Background:

• Micronuclei (MN) are markers of chromosomal instability and can indicate increased cancer risk or aggressive tumor subtypes.
• Monitoring MN in circulating white blood cells (cWBCs) and tumor cells is challenging due to their rarity and dynamic formation.
• Circulating Stromal Cells (CStCs) offer a potential new source for MN detection in peripheral blood.

Purpose of the Study:

• To investigate the presence and prognostic significance of MN in CStCs of advanced colorectal cancer (CRC) patients.
• To determine if MN formation in CStCs is associated with genotoxic therapies or clinical outcomes.

Main Methods:

• A prospective pilot study analyzed 7.5 mL of peripheral blood from 25 advanced CRC patients.
• Micronuclei were identified as DAPI+ structures (<3 µm) within the cytoplasm of CStCs.
• MN presence was compared to genotoxic therapy, tumor stage, progression-free survival (PFS), and overall survival (OS).

Main Results:

• Micronuclei were detected in 44% of CStCs.
• MN presence in CStCs was not associated with genotoxic therapies or tumor stage.
• MN in CStCs independently predicted significantly worse PFS (HR=17.2) and OS (HR=70.3).
• MN formation correlated with tumor response and appeared independent of chemotherapy induction.

Conclusions:

• Micronuclei formation in CStCs of CRC patients represents an underlying biological mechanism, not directly induced by chemotherapeutic genotoxins.
• The presence of MN in CStCs is a strong, independent prognostic biomarker for poor clinical outcomes in advanced CRC.
• Sequential monitoring of MN in CStCs may offer a non-invasive method for predicting patient prognosis.