Faculty, Staff and Student Publications

Publication Date

2-1-2025

Journal

Biomarkers

DOI

10.1080/1354750X.2024.2447089

PMID

39761813

PMCID

PMC11856746

PubMedCentral® Posted Date

2-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations were more prevalent in LOCRC. Stratification by tumor site and MSI status highlighted significant location- and age-specific molecular differences, such as increased KRAS and CTNNB1 mutations in right-sided EOCRC and higher BRAF prevalence in MSI-H LOCRC (47% vs. 6.7%, p < 0.001). Additionally, co-occurrence analysis revealed unique mutational networks in EOCRC MSS, including significant co-occurrences of FBXW7 with NOTCH3, RB1, and PIK3R1.

Conclusion: This study highlights the significance of age-specific molecular profiling, offering insights into the unique biology of EOCRC and potential clinical applications.

Keywords

Humans, Colorectal Neoplasms, Female, Middle Aged, Male, Mutation, Age of Onset, Aged, Proto-Oncogene Proteins B-raf, Adult, beta Catenin, Proto-Oncogene Proteins p21(ras), Tumor Suppressor Protein p53, Receptor, Notch1, Smad4 Protein, F-Box-WD Repeat-Containing Protein 7, Biomarkers, Tumor, Microsatellite Instability, Ubiquitin-Protein Ligases, Early-onset colorectal cancer, Late-onset colorectal cancer, Next-generation sequencing, NGS, APC, TP53

Published Open-Access

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