Predominant Serrated Molecular Signature in Postcolonoscopy Colorectal Cancer: A Systematic Review and Meta-Analysis

Jen-Hao Yeh ^1,2, Sin-Hua Moi ^1,3,4, Chia-Chi Chen ⁵

¹Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da DaChang Hospital, I-Shou University, Kaohsiung, Taiwan.
³Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁶Divsion of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan.
⁷School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁹Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁰Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹¹Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

⁰Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

The American Journal of Gastroenterology +

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July 23, 2025

View abstract on PubMed

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.

Keywords:

biomarker colonoscopy colorectal cancer postcolonoscopy colorectal cancer sessile serrated lesion