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. 2025 Jul 1;16(10):3024–3039. doi: 10.7150/jca.111828

Table 2.

Comprehensive Histological, Genetic, and Epigenetic Biomarkers

First author/s, year Biomarker Marker type Diagnostic or prognostic utility Refs.
Popat S et al., 2005 Microsatellite Instability (MSI) Genetic Indicates better prognosis and resistance to monotherapy with fluoropyrimidines; associated with immune infiltration and better survival outcomes. 41
Zhu G et al., 2021 - Yamashita S et al., 2028 KRAS/NRAS Genetic Associated with poor prognosis; predicts resistance to anti-EGFR therapies; frequent in metastatic colorectal cancer. 45, 47
Tabernero J et al., 2021 BRAF V600E Genetic Linked to high-grade tumors with poor prognosis; prevalent in right-sided tumors and older patients. 51
Tran B et al., 2011 Invasion of Lymph Nodes Histological Predicts recurrence risk and poor outcomes; reflects aggressive local invasion. 69
Liao X et al., 2012 PIK3CA Genetic Associated with poor prognosis; mutations in exons 9 and 20 predict worse survival; aspirin use may improve outcomes. 53
Fakih M et al., 2024 KRAS G12C Genetic Predicts response to therapies targeting KRAS mutations; improved progression-free survival with targeted therapy combinations. 46
Zhang L et al., 2017 - Liang J et al., 2013 APC Mutation Genetic Essential in tumor progression; linked to instability in WNT signaling pathway; predictive of worse outcomes in advanced disease. 38, 39
Wright M et al., 2017 Hypermethylation (MLH1) Epigenetic Correlates with microsatellite instability; better prognosis in tumors with hypermethylation of MLH1 promoter. 62
Hur K et al., 2014 Hypomethylation (LINE-1) Epigenetic Linked to aggressive tumor behavior and poor prognosis; found in advanced colorectal cancer. 66
Ilie-Petrov et al., 2023 CDX2 Histological/Epigenetic Expression correlates with better survival; loss linked to tumor progression and worse outcomes. 68

The table on histological markers highlights their critical role in colorectal cancer (CRC) diagnosis, prognosis, and treatment planning. It includes key factors such as tumor differentiation grade, depth of submucosal invasion, lymph node involvement, and specific molecular markers like cytokeratins (e.g., CK20). Additionally, markers like Ki-67, p16, and p21 provide insights into tumor proliferation and aggressiveness, guiding risk stratification and therapeutic strategies.