Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Even though the screening programs have decreased the incidence rates, the prognosis for CRC varies depending on the stage at diagnosis. Thus, early diagnosis is still a big challenge due to screening methods, and subsequent diagnosis is not very sensitive.Methods: In this work, LC-MS-based metabolomics, a powerful and sensitive tool to study complex dynamic changes, was used to analyze 211 human fecal samples from control individuals (CTRL), adenoma (AA), and CRC patients.Results: Multivariate and univariate statistical analysis highlighted cholesteryl esters (CEs) and fecal haemoglobin, quantified by fecal immunochemical test (FIT), as relevant biomarkers that clearly differentiate CRC from AA and CTRL. Predictive models based on random forest and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) demonstrate that CEs, together with FIT measurement, improved the CRC and CTRL classification, but not AA. This study revealed that the AA group is a transitional stage with high heterogeneity. The increased tendency observed in CEs from CTRL to CRC might be related to the imbalance of cholesterol homeostasis due to cancer cells requiring a high cholesterol level for cell development and proliferation. The free cholesterol is probably obtained from CEs, as it is the most cost/effective way to obtain the needed cholesterol.Conclusions: The accumulation of CEs is produced by two possible approaches: (1) dysfunction of cholesterol absorption in the small intestine and/or (2) transported inside exosomes from cell to cell to promote proliferation.
背景/目的：结直肠癌是全球范围内最常见的癌症之一。尽管筛查项目已降低了其发病率，但结直肠癌的预后仍取决于诊断时的分期。由于现有筛查方法的敏感性有限，早期诊断仍面临重大挑战。 方法：本研究采用基于液相色谱-质谱联用技术的代谢组学方法，这一强大而灵敏的工具可用于研究复杂的动态变化。研究共分析了211份人类粪便样本，包括健康对照者、腺瘤患者及结直肠癌患者。 结果：多变量与单变量统计分析显示，胆固醇酯和粪便血红蛋白（通过粪便免疫化学试验定量）是区分结直肠癌与腺瘤及健康对照的关键生物标志物。基于随机森林的预测模型及受试者工作特征曲线下面积分析表明，胆固醇酯结合粪便免疫化学试验可提升结直肠癌与健康对照的分类准确性，但对腺瘤的鉴别效果有限。本研究发现腺瘤组是一个具有高度异质性的过渡阶段。从健康对照到结直肠癌患者中观察到的胆固醇酯升高趋势，可能与癌细胞为满足其发育和增殖所需的高胆固醇水平导致的胆固醇稳态失衡有关。游离胆固醇很可能来源于胆固醇酯，因为这是获取所需胆固醇最具成本效益的方式。 结论：胆固醇酯的积累可能通过两种途径产生：（1）小肠胆固醇吸收功能障碍，和/或（2）通过外泌体在细胞间转运以促进增殖。
肿瘤(癌症)患者之家