Alshenaifi Jumanah Yousef, Vetere Guglielmo, Maddalena Giulia, Yousef Mahmoud, White Michael G, Shen John Paul, Vilar Eduardo, Parseghian Christine, Dasari Arvind, Morris Van Karlyle, Huey Ryan, Overman Michael J, Wolff Robert, Raghav Kanwal P, Willis Jason, Alfaro Kristin, Futreal Andy, You Y Nancy, Kopetz Scott
Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Biomarkers. 2025 Feb;30(1):64-76. doi: 10.1080/1354750X.2024.2447089. Epub 2025 Jan 9.
Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.
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).
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 (74% vs. 68%, < 0.01) and (17% vs. 14%, = 0.015), while (5% vs. 11%, < 0.001) and (2.7% vs. 4.1%, = 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 and mutations in right-sided EOCRC and higher prevalence in MSI-H LOCRC (47% vs. 6.7%, < 0.001). Additionally, co-occurrence analysis revealed unique mutational networks in EOCRC MSS, including significant co-occurrences of with , , and .
This study highlights the significance of age-specific molecular profiling, offering insights into the unique biology of EOCRC and potential clinical applications.
近几十年来，50岁之前的结直肠癌（CRC）发病率和死亡率一直在惊人地上升。
本研究使用了一个由10000名患者组成的队列，调查了早发性（EOCRC，<50岁）与晚发性（LOCRC，≥50岁）CRC的临床、突变和共突变特征。
EOCRC与亚洲和西班牙裔患者的患病率较高、直肠或左侧肿瘤（72%对59%）以及晚期疾病相关。分子分析揭示了突变模式的差异，EOCRC的 （74%对68%，<0.01）和 （17%对14%，=0.015）频率较高，而 （5%对11%，<0.001）和 （2.7%对4.1%，=0.01）突变在LOCRC中更为普遍。按肿瘤部位和MSI状态分层突出了显著的位置和年龄特异性分子差异，如右侧EOCRC中 和 突变增加，以及MSI-H LOCRC中 患病率较高（47%对6.7%，<0.001）。此外，共现分析揭示了EOCRC MSS中独特的突变网络，包括 与 、 和 的显著共现。
本研究强调了年龄特异性分子谱分析的重要性，为EOCRC的独特生物学特性和潜在临床应用提供了见解。
