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Predominant Serrated Molecular Signature in Postcolonoscopy Colorectal Cancer: A Systematic Review and Meta-Analysis.
Jen-Hao Yeh1,2, Sin-Hua Moi1,3,4, Chia-Chi Chen5
1Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
The American Journal of Gastroenterology
|July 23, 2025
Summary
Postcolonoscopy colorectal cancers (PCCRCs) are molecularly distinct from sporadic colorectal cancers (SCRC), often showing microsatellite instability and BRAF mutations. Improving serrated lesion detection may enhance colorectal cancer screening effectiveness.
Area of Science:
- Gastroenterology
- Molecular Oncology
- Cancer Research
Background:
- Postcolonoscopy colorectal cancers (PCCRCs) represent a critical challenge in colorectal cancer (CRC) screening due to missed lesions and incomplete polypectomy.
- The molecular underpinnings of PCCRCs remain incompletely understood, hindering targeted prevention and management strategies.
Purpose of the Study:
- To systematically review and analyze the molecular characteristics of PCCRCs.
- To compare the molecular profiles of PCCRCs with sporadic colorectal cancers (SCRC).
Main Methods:
- Comprehensive literature search of PubMed, Embase, and Cochrane Library databases up to April 2024.
- Inclusion of studies examining molecular features: microsatellite instability (MSI), CpG island methylation phenotype (CIMP), genetic mutations (BRAF, KRAS), and chromosomal alterations.
- Meta-analysis of data from 15 studies, including 2,143 PCCRC and 19,036 SCRC cases.
Main Results:
- PCCRCs are associated with older age and more proximal tumor location compared to SCRC.
- Molecularly, PCCRCs exhibit higher rates of MSI, CIMP, and BRAF mutations, but lower rates of KRAS mutations.
- MSI strongly correlates with BRAF mutation and proximal lesions in PCCRCs.
- While overall survival is similar to SCRC, PCCRCs show worse survival than screening-detected CRCs.
Conclusions:
- PCCRCs share molecular features with the serrated pathway of colorectal cancer development, distinguishing them from SCRC.
- Targeted enhancement of serrated lesion detection during colonoscopy may improve CRC screening efficacy and reduce PCCRC incidence.
